Current Progresses and Challenges of Immunotherapy in Triple-Negative Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Immune Checkpoint Inhibition: Therapeutic Strategies
2.1. PD-1/PD-L1 Axis
2.2. CTLA-4 and Dual Checkpoint Inhibition
2.3. Next Generation Immune Modulatory Targets
3. Factors Affecting the Efficacy of Immune Checkpoint Inhibitors
3.1. Dysregulated Tumor Vasculature
3.2. Interleukin-8 and CXCR1/CXCR2
3.3. CD73 Expression
3.4. Long Non-Coding RNAs and Microsatellite Instability
3.5. Wnt and YAP Signaling
3.6. Nanoparticle Platforms as a Delivery System
4. Cancer Cell Antigens: Potential Therapeutic Targets
4.1. Cancer-Testis Antigens
4.2. Tumor Antigens, Cancer Vaccine, and Oncolytic Virus
5. Chimeric Antigen Receptor T-Cell Therapy
6. Immunotherapy and Metabolism
6.1. Metabolic Reprogramming in TNBC
6.2. Aerobic Glycolysis and Immunosuppression
6.3. Glutamine Metabolism in Immunosuppression
6.4. Lipid Metabolism in Immunosuppression
6.5. Autophagy in TNBC
6.6. Interplay of HIF-1α in Cancer Metabolism and Immunosurveillance
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics. CA Cancer J. Clin. 2020, 70, 7–30. [Google Scholar] [CrossRef] [PubMed]
- Sharma, R. Breast cancer incidence, mortality and mortality-to-incidence ratio (MIR) are associated with human development, 1990–2016: Evidence from Global Burden of Disease Study 2016. Breast Cancer 2019, 26, 428–445. [Google Scholar] [CrossRef] [PubMed]
- Dent, R.; Trudeau, M.; Pritchard, K.I.; Hanna, W.M.; Kahn, H.K.; Sawka, C.A.; Lickley, L.A.; Rawlinson, E.; Sun, P.; Narod, S.A. Triple-Negative breast cancer: Clinical features and patterns of recurrence. Clin. Cancer Res. 2007, 13, 4429–4434. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Garrido-Castro, A.C.; Lin, N.U.; Polyak, K. Insights into molecular classifications of triple-negative breast cancer: Improving patient selection for treatment. Cancer Discov. 2019, 9, 176–198. [Google Scholar] [CrossRef] [Green Version]
- Golan-Vered, Y.; Pud, D. Chemotherapy-Induced neuropathic pain and its relation to cluster symptoms in breast cancer patients treated with Paclitaxel. Pain Pract. 2013, 13, 46–52. [Google Scholar] [CrossRef]
- Dean, M.; Fojo, T.; Bates, S. Tumour stem cells and drug resistance. Nat. Rev. Cancer 2005, 5, 275–284. [Google Scholar] [CrossRef]
- Li, K.; Lai, H. TanshinoneIIA enhances the chemosensitivity of breast cancer cells to doxorubicin through down-regulating the expression of MDR-related ABC transporters. Biomed. Pharm. 2017, 96, 371–377. [Google Scholar] [CrossRef]
- Han, J.; Lim, W.; You, D.; Jeong, Y.; Kim, S.; Lee, J.E.; Shin, T.H.; Lee, G.; Park, S. Chemoresistance in the human triple-negative breast cancer cell line MDA-MB-231 induced by doxorubicin gradient is associated with epigenetic alterations in histone deacetylase. J. Oncol. 2019, 2019, 1345026. [Google Scholar] [CrossRef]
- Makhoul, I.; Atiq, M.; Alwbari, A.; Kieber-Emmons, T. Breast Cancer immunotherapy: An update. Breast Cancer Basic Clin. Res. 2018, 12, 1178223418774802. [Google Scholar] [CrossRef]
- Kim, Y.-A.; Lee, H.J.; Heo, S.-H.; Park, H.S.; Park, S.Y.; Bang, W.; Song, I.H.; Park, I.A.; Gong, G. MxA expression is associated with tumor-infiltrating lymphocytes and is a prognostic factor in triple-negative breast cancer. Breast Cancer Res. Treat. 2016, 156, 597–606. [Google Scholar] [CrossRef] [PubMed]
- Kitano, A.; Ono, M.; Yoshida, M.; Noguchi, E.; Shimomura, A.; Shimoi, T.; Kodaira, M.; Yunokawa, M.; Yonemori, K.; Shimizu, C.; et al. Tumour-infiltrating lymphocytes are correlated with higher expression levels of PD-1 and PD-L1 in early breast cancer. ESMO Open 2017, 2, e000150. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ali, H.R.; Glont, S.-E.; Blows, F.M.; Provenzano, E.; Dawson, S.-J.; Liu, B.; Hiller, L.; Dunn, J.; Poole, C.J.; Bowden, S.; et al. PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes. Ann. Oncol. 2015, 26, 1488–1494. [Google Scholar] [CrossRef] [PubMed]
- Vikas, P.; Borcherding, N.; Zhang, W. The clinical promise of immunotherapy in triple-negative breast cancer. Cancer Manag. Res. 2018, 10, 6823–6833. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mori, H.; Kubo, M.; Yamaguchi, R.; Nishimura, R.; Osako, T.; Arima, N.; Okumura, Y.; Okido, M.; Yamada, M.; Kai, M.; et al. The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer. Oncotarget 2017, 8, 15584–15592. [Google Scholar] [CrossRef] [Green Version]
- Loi, S.; Michiels, S.; Salgado, R.; Sirtaine, N.; Jose, V.; Fumagalli, D.; Kellokumpu-Lehtinen, P.L.; Bono, P.; Kataja, V.; Desmedt, C.; et al. Tumour infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: Results from the FinHER trail. Ann. Oncol. 2014, 25, 1544–1550. [Google Scholar] [CrossRef] [PubMed]
- Lee, S.E.; Park, H.Y.; Lim, S.D.; Han, H.S.; Yoo, Y.B.; Kim, W.S. Concordance of programmed death-ligand 1 expression between SP142 and 22C3/SP263 assays in triple-negative breast cancer. J. Breast Cancer 2020, 23, 303–313. [Google Scholar] [CrossRef] [PubMed]
- Bardhan, K.; Anagnostou, T.; Boussiotis, V.A. The PD1:PD-L1/2 pathway from discovery to clinical implementation. Front. Immunol. 2016, 7, 550. [Google Scholar] [CrossRef] [Green Version]
- Lipson, E.J.; Forde, P.M.; Hammers, H.-J.; Emens, L.A.; Taube, J.M.; Topalian, S.L. Antagonists of PD-1 and PD-L1 in cancer treatment. Semin. Oncol. 2015, 42, 587–600. [Google Scholar] [CrossRef] [Green Version]
- Mittendorf, E.A.; Philips, A.V.; Meric-Bernstam, F.; Qiao, N.; Wu, Y.; Harrington, S.; Su, X.; Wang, Y.; Gonzalez-Angulo, A.M.; Akcakanat, A.; et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol. Res. 2014, 2, 361–370. [Google Scholar] [CrossRef] [Green Version]
- Goodman, A.M.; Piccioni, D.; Kato, S.; Boichard, A.; Wang, H.-Y.; Frampton, G.; Lippman, S.M.; Connelly, C.; Fabrizio, D.; Miller, V.; et al. Prevalence of PDL1 amplification and preliminary response to immune checkpoint blockade in solid tumors. JAMA Oncol. 2018, 4, 1237–1244. [Google Scholar] [CrossRef] [Green Version]
- Barrett, M.T.; Anderson, K.S.; Lenkiewicz, E.; Andreozzi, M.; Cunliffe, H.E.; Klassen, C.L.; Dueck, A.C.; McCullough, A.E.; Reddy, S.K.; Ramanathan, R.K.; et al. Genomic amplification of 9p24.1 targeting JAK2, PD-L1 and PD-L2 is enriched in high-risk triple negative breast cancer. Oncotarget 2015, 6, 26483–26493. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sabatier, R.; Finetti, P.; Mamessier, E.; Adelaide, J.; Chaffanet, M.; Ali, H.R.; Viens, P.; Caldas, C.; Birnbaum, D.; Bertucci, F. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget 2015, 6, 5449–5464. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Emens, L.A.; Cruz, C.; Eder, J.P.; Braiteh, F.; Chung, C.; Tolaney, S.M.; Kuter, I.; Nanda, R.; Cassier, P.A.; Delord, J.P.; et al. Long-term clinical outcomes and biomarker analyses of atezolizumab therapy for patients with metastatic triple-negative breast cancer: A phase 1 study. JAMA Oncol. 2019, 5, 74–82. [Google Scholar] [CrossRef] [PubMed]
- Schmid, P.; Adams, S.; Rugo, H.S.; Schneeweiss, A.; Barrios, C.H.; Iwata, H.; Diéras, V.; Hegg, R.; Im, S.A.; Wright, G.S.; et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N. Engl. J. Med. 2018, 379, 2108–2121. [Google Scholar] [CrossRef] [PubMed]
- Adams, S.; Schmid, P.; Rugo, H.; Winer, E.; Loirat, D.; Awada, A.; Cescon, D.; Iwata, H.; Campone, M.; Nanda, R.; et al. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: Cohort A of the phase II KEYNOTE-086 study. Ann. Oncol. 2019, 30, 397–404. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Adams, S.; Loi, S.; Toppmeyer, D.; Cescon, D.W.; De Laurentiis, M.D.; Nanda, R.; Winer, E.P.; Mukai, H.; Tamura, K.; Armstrong, A.; et al. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: Cohort B of the phase II KEYNOTE-086 study. Ann. Oncol. 2019, 30, 405–411. [Google Scholar] [CrossRef] [Green Version]
- Schmid, P.; Cortes, J.; Pusztai, L.; McArthur, H.; Kümmel, S.; Bergh, J.; Denkert, C.; Park, Y.H.; Hui, R.; Harbeck, N.; et al. Pembrolizumab for early-triple negative breast cancer. N. Engl. J. Med. 2020, 382, 810–821. [Google Scholar] [CrossRef] [PubMed]
- Vonderheide, R.H.; Domchek, S.M.; Clark, A.S. Immunotherapy for breast cancer: What are we missing? Clin. Cancer Res. 2017, 23, 2640–2646. [Google Scholar] [CrossRef] [Green Version]
- Vilariño, N.; Bruna, J.; Kalofonou, F.; Anastopoulou, G.G.; Argyriou, A.A. Immune-Driven pathogenesis of neurotoxicity after exposure of cancer patients to immune checkpoint inhibitors. Int. J. Mol. Sci. 2020, 21, 5774. [Google Scholar] [CrossRef]
- Hendry, S.; Salgado, R.; Gevaert, T.; Russell, P.A.; John, T.; Thapa, B.; Christie, M.; van de Vijver, K.; Estrada, V.M.; Gonzalez-Ericsson, P.I.; et al. Assessing tumor infiltrating lymphocytes in solid tumors: A practical review for pathologists and proposal for a standardized method from the International Immuno-Oncology Biomarkers Working Group Part 1: Assessing the host immune response, TILs in invasive breast carcinoma and ductal carcinoma in situ, metastatic tumor deposits and areas for further research. Adv. Anat. Pathol. 2017, 24, 235–251. [Google Scholar] [CrossRef] [Green Version]
- Spigel, D.; Marinis, F.D.; Giaccone, G.; Reinmuth, N.; Vergnenegre, A.; Barrios, C.H.; Morise, M.; Felip, E.; Andric, Z.; Geatic, S.; et al. IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1-selected NSCLC. Ann. Oncol. 2019, 30, 915. [Google Scholar] [CrossRef]
- Miles, D.W.; Gligorov, J.; André, F.; Cameron, D.; Schneeweiss, A.; Barrios, C.H.; Xu, B.; Wardley, A.M.; Kaen, D.; Andrade, L.; et al. LBA15–Primary results from IMpassion131, a double-blind placebo-controlled randomized phase III trial of first-line paclitaxel (PAC) ± atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC). Ann. Oncol. 2020, 31, S1147. [Google Scholar] [CrossRef]
- Kwa, M.J.; Adams, S. Checkpoint inhibitors in triple-negative breast cancer (TNBC): Where to go from here. Cancer 2018, 124, 2086–2103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cortés, J.; Lipatov, O.; Im, S.-A.; Gonçalves, A.; Lee, K.; Schmid, P.; Tamura, K.; Testa, L.; Witzel, I.; Ohtani, S.; et al. KEYNOTE-119: Phase III study of pembrolizumab (pembro) versus single-agent chemotherapy (chemo) for metastatic triple negative breast cancer (mTNBC). Ann. Oncol. 2019, 30, v859–v860. [Google Scholar] [CrossRef]
- Mirabile, A.; Brioschi, E.; Ducceschi, M.; Piva, S.; Lazzari, C.; Bulotta, A.; Viganò, M.G.; Petrella, G.; Gianni, L.; Gregorc, V. PD-1 inhibitors-related neurological toxicities in patients with non-small-cell lung cancer: A literature review. Cancers 2019, 11, 296. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fellner, A.; Makranz, C.; Lotem, M.; Bokstein, F.; Taliansky, A.; Rosenberg, S.; Blumenthal, D.; Mandel, J.; Fichman, S.; Kogan, E.; et al. Neurologic complications of immune checkpoint inhibitors. J. Neuro-Oncol. 2018, 137, 601–609. [Google Scholar] [CrossRef]
- Nair, V.S.; Elkord, E. Immune checkpoint inhibitors in cancer therapy: A focus on T-regulatory cells. Immunol. Cell Biol. 2018, 96, 21–33. [Google Scholar] [CrossRef]
- Walunas, T.L.; Lenschow, D.J.; Bakker, C.Y.; Linsley, P.S.; Freeman, G.J.; Green, J.M.; Thompson, C.B.; Bluestone, J.A. CTLA-4 can function as a negative regulator of T cell activation. Immunity 1994, 1, 405–413. [Google Scholar] [CrossRef]
- Buchbinder, E.I.; Desai, A. CTLA-4 and PD-1 pathways: Similarities, differences, and implications of their inhibition. Am. J. Clin. Oncol. 2016, 39, 98–106. [Google Scholar] [CrossRef] [Green Version]
- Krummey, S.M.; Hartigan, C.R.; Liu, D.; Ford, M.L. CD-28-Dependent CTLA-4 expression fine-tunes the activation of human Th17 cells. iScience 2020, 23, 100912. [Google Scholar] [CrossRef]
- Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J.J.; Cowey, C.L.; Lao, C.D.; Schadendorf, D.; Dummer, R.; Smylie, M.; Rutkowski, P.; et al. Combined nivolumab and ipilimumab or monotherapy in previously untreated melanoma. N. Engl. J. Med. 2015, 373, 23–34. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kooshkaki, O.; Derakhshani, A.; Hosseinkhani, N.; Torabi, M.; Safaei, S.; Brunetti, O.; Racanelli, V.; Silvestris, N.; Baradaran, B. Combination of ipilimumab and nivolumab in cancers: From clinical practice to ongoing clinical trials. Int. J. Mol. Sci. 2020, 21, 4427. [Google Scholar] [CrossRef] [PubMed]
- Antonia, S.J.; López-Martin, J.A.; Bendell, J.; Ott, P.A.; Taylor, M.; Eder, J.P.; Jäger, D.; Pietanza, M.C.; Le, D.T.; de Braud, F.; et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): A multicenter, open-label, phase 1/2 trial. Lancet Oncol. 2016, 17, 883–895. [Google Scholar] [CrossRef] [Green Version]
- Reck, M.; Ciuleanu, T.-E.; Dols, M.C.; Schenker, M.; Zurawski, B.; Menezes, J.; Richardet, E.; Bennouna, J.; Felip, E.; Juan-Vidal, O.; et al. Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy (chemo) vs 4 cycles chemo as first-line (1L) treatment (tx) for stage IV/recurrent non-small cell lung cancer (NSCLC): CheckMate 9LA. J. Clin. Oncol. 2020, 38, 9501. [Google Scholar] [CrossRef]
- Amaria, R.N.; Reddy, S.M.; Tawbi, H.A.; Davies, M.A.; Ross, M.I.; Glitza, I.C.; Cormier, J.M.; Lewis, C.; Hwu, W.-J.; Hanna, E.; et al. Neoedjuvant immune checkpoint blockade in high-risk resectable melanoma. Nat. Med. 2018, 24, 1649–1654. [Google Scholar] [CrossRef]
- Santa-Maria, C.A.; Kato, T.; Park, J.-H.; Flaum, L.E.; Jain, S.; Tellez, C.; Stein, R.M.; Shah, A.N.; Gross, L.; Uthe, R.; et al. Durvalumab and tremelimumab in metastatic breast cancer (MBC): Immunotherapy and immunopharmacogenomic dynamics. J. Clin. Oncol. 2017, 35, 3052. [Google Scholar] [CrossRef]
- Ager, C.R.; Reilley, M.J.; Nicholas, C.; Bartkowiak, T.; Jaiswal, A.R.; Curran, M.A. Intratumoral STING activation with T-cell checkpoint modulation generates systemic antitumor immunity. Cancer Immunol. Res. 2017, 5, 676–684. [Google Scholar] [CrossRef] [Green Version]
- Tan, Y.S.; Sansanaphongpricha, K.; Xie, Y.; Donnelly, C.R.; Luo, X.; Heath, B.R.; Zhao, X.; Bellile, E.L.; Hu, H.; Chen, H.; et al. Mitigating SOX2-potentiated immune escape of head and neck squamous cell carcinoma with a STING-inducing nanosatellite vaccine. Clin. Cancer Res. 2018, 24, 4242–4255. [Google Scholar] [CrossRef] [Green Version]
- Harding, S.M.; Benci, J.L.; Irianto, J.; Discher, D.E.; Minn, A.J.; Greenberg, R.A. Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature 2017, 548, 466–470. [Google Scholar] [CrossRef] [Green Version]
- Liu, Y.; Zheng, P. Preserving the CTLA-4 checkpoint for safer and more effective cancer immunotherapy. Trends Pharmacol. Sci. 2019, 41, 4–12. [Google Scholar] [CrossRef]
- Zhang, Y.; Du, X.; Liu, M.; Tang, F.; Zhang, P.; Ai, C.; Fields, J.K.; Sundberg, E.J.; Latinovic, O.S.; Devenport, M.; et al. Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy. Cell Res. 2019, 29, 609–627. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tivol, E.A.; Borriello, F.; Schweitzer, A.; Lynch, W.P.; Bluestone, J.A.; Sharpe, A.H. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 1995, 3, 541–547. [Google Scholar] [CrossRef] [Green Version]
- Gough, S.C.L.; Walker, L.S.K.; Sansom, D.M. CTLA4 gene polymorphism and autoimmunity. Immunol. Rev. 2005, 204, 102–115. [Google Scholar] [CrossRef] [PubMed]
- Weber, J.; Mandalà, M.; Del Vecchio, M.; Gogas, H.; Arance, A.M.; Cowey, C.L.; Dalle, S.; Schenker, M.; Chiarion-Sileni, V.; Marquez-Rodas, I.; et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N. Engl. J. Med. 2017, 377, 1824–1835. [Google Scholar] [CrossRef]
- Calabrese, L.H.; Calabrese, C.; Cappelli, L.C. Rheumatic immune-related adverse events from cancer immunotherapy. Nat. Rev. Rheumatol. 2018, 14, 569–579. [Google Scholar] [CrossRef]
- Vétizou, M.; Pitt, J.M.; Daillère, R.; Lepage, P.; Waldschmitt, N.; Flament, C.; Rusakiewicz, S.; Routy, B.; Roberti, M.P.; Duong, C.P.M.; et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 2015, 350, 1079–1084. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; Sun, J.; Liu, L.N.; Flies, D.B.; Nie, X.; Toki, M.; Zhang, J.; Song, C.; Zarr, M.; Zhou, X.; et al. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nat. Med. 2019, 25, 656–666. [Google Scholar] [CrossRef]
- Cao, G.; Xiao, Z.; Yin, Z. Normalization cancer immunotherapy: Blocking Siglec-15! Signal Tranduct. Target Ther. 2019, 4, 10. [Google Scholar] [CrossRef] [Green Version]
- Solomon, B.L.; Garrido-Laguna, I. TIGIT: A novel immunotherapy target moving from bench to bedside. Cancer Immunol. Immunother. 2018, 67, 1659–1667. [Google Scholar] [CrossRef]
- Pandey, A.K.; Chauvin, J.M.; Brufsky, A.; Pagliano, O.; Ka, M.; Menna, C.; McAuliffe, P.; Zarour, H. Abstract P5-04-28: Targeting TIGIT and PD-1 in triple negative breast cancer. Poster Sess. Abstr. 2020, 80. [Google Scholar] [CrossRef]
- Iguchi-Manaka, A.; Okumura, G.; Ichioka, E.; Kiyomatsu, H.; Ikeda, T.; Bando, H.; Shibuya, A.; Shibuya, K. High expression of soluble CD155 in estrogen receptor-negative breast cancer. Breast Cancer 2020, 27, 92–99. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sanchez-Correa, B.; Valhondo, I.; Hassouneh, F.; Lopez-Sejas, N.; Pera, A.; Bergua, J.M.; Arcos, M.J.; Bañas, H.; Casas-Avilés, I.; Durán, E.; et al. DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel immune checkpoints for natural killer cell-based cancer immunotherapy. Cancers 2019, 11, 877. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Harjunpää, H.; Blake, S.J.; Ahern, E.; Allen, S.; Liu, J.; Yan, J.; Lutzky, V.; Takeda, K.; Aguilera, A.R.; Guillerey, C.; et al. Deficiency of host CD96 and PD-1 or TIGIT enhances tumor immunity without significantly compromising immune homeostasis. OncoImmunology 2018, 7, e1445949. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Saleh, R.; Toor, S.M.; Khalaf, S.; Elkord, E. Toor breast cancer cells and PD-1/PD-L1 blockade upregulate the expression of PD-1, CTLA-4, TIM-3 and LAG-3 immune checkpoints in CD4+ T cells. Vaccines 2019, 7, 149. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Piconese, S.; Valzasina, B.; Colombo, M.P. OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection. J. Exp. Med. 2008, 205, 825–839. [Google Scholar] [CrossRef] [Green Version]
- Chester, C.; Sanmamed, M.F.; Wang, J.; Melero, I. Immunotherapy targeting 4-1BB: Mechanistic rationale, clinical results, and future strategies. Blood 2018, 131, 49–57. [Google Scholar] [CrossRef]
- Schrand, B.; Berezhnoy, A.; Brenneman, R.; Williams, A.; Levay, A.; Kong, L.-Y.; Rao, G.; Zhou, S.; Heimberger, A.B.; Gilboa, E. Targeting 4-1BB costimulation to the tumor stroma with bispecific aptamer conjugates enhances the therapeutic index of tumor immunotherapy. Cancer Immunol. Res. 2014, 2, 867–877. [Google Scholar] [CrossRef] [Green Version]
- Yap, T.A.; Burris, H.A.; Kummar, S.; Falchook, G.S.; Pachynski, R.K.; Lorusso, P.; Tykodi, S.S.; Gibney, G.T.; Gainor, J.F.; Rahma, O.E.; et al. ICONIC: Biologic and clinical activity of first in class ICOS agonist antibody JTX-2011 +/- nivolumab (nivo) in patients (pts) with advanced cancers. J. Clin. Oncol. 2018, 36, 3000. [Google Scholar] [CrossRef]
- Emens, L.A. Breast cancer immunotherapy: Facts and hopes. Clin. Cancer Res. 2018, 24, 511–520. [Google Scholar] [CrossRef] [Green Version]
- Leisha, A.E.; Emens, L.A. Chemotherapy and tumor immunity: An unexpected collaboration. Front. Biosci. 2008, 13, 249–257. [Google Scholar] [CrossRef] [Green Version]
- Bielenberg, D.R.; Zetter, B.R. The contribution of angiogenesis to the process of metastasis. Cancer J. 2015, 21, 267–273. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zimna, A.; Kurpisz, M. Hypoxia-Inducible factor-1 in physiological and pathophysiological angiogenesis: Applications and therapies. BioMed Res. Int. 2015, 2015, 549412. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liao, D.; Johnson, R.S. Hypoxia: A key regulator of angiogenesis in cancer. Cancer Metastasis Rev. 2007, 26, 281–290. [Google Scholar] [CrossRef] [PubMed]
- Vishwanatha, J.K.; Castañeda-Gill, J.M. Antiangiogenic mechanisms and factors in breast cancer treatment. J. Carcinog. 2016, 15, 1. [Google Scholar] [CrossRef] [PubMed]
- Fukumura, D.; Kloepper, J.; Amoozgar, Z.; Duda, D.G.; Jain, R.K. Enhancing cancer immunotherapy using antiangiogenics: Opportunities and challenges. Nat. Rev. Clin. Oncol. 2018, 15, 325–340. [Google Scholar] [CrossRef] [PubMed]
- Schmittnaegel, M.; Rigamonti, N.; Kadioglu, E.; Cassará, A.; Rmili, C.W.; Kiialainen, A.; Kienast, Y.; Mueller, H.-J.; Ooi, C.-H.; Laoui, D.; et al. Dual angiopoietin-2 and VEGFA inhibition elicits antitumor activity that is enhanced by PD-1 checkpoint blockade. Sci. Transl. Med. 2017, 9, eaak9670. [Google Scholar] [CrossRef] [PubMed]
- Kammertoens, T.; Friese, C.; Arina, A.; Idel, C.; Briesemeister, D.; Rothe, M.; Ivanov, A.; Szymborska, A.; Patone, G.; Kunz, S.; et al. Tumour ischaemia by interferon-γ resembles physiological blood vessel regression. Nat. Cell Biol. 2017, 545, 98–102. [Google Scholar] [CrossRef]
- Allen, E.; Jabouille, A.; Rivera, L.B.; Lodewijckx, I.; Missiaen, R.; Steri, V.; Feyen, K.; Tawney, J.; Hanahan, D.; Michael, I.P.; et al. Combined antiangiogenic and anti-PD-L1 therapy stimulates tumor immunity through HEV formation. Sci. Transl. Med. 2017, 9, eaak9679. [Google Scholar] [CrossRef] [Green Version]
- Tian, L.; Goldstein, A.; Wang, H.; Lo, H.C.; Kim, I.S.; Welte, T.; Sheng, K.; Dobrolecki, L.E.; Zhang, X.; Putluri, N.; et al. Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming. Nat. Cell Biol. 2017, 544, 250–254. [Google Scholar] [CrossRef]
- Zheng, X.; Fang, Z.; Liu, X.; Deng, S.; Zhou, P.; Wang, X.; Zhang, C.; Yin, R.; Hu, H.; Chen, X.; et al. Increased vessel perfusion predicts the efficacy of immune checkpoint blockade. J. Clin. Investig. 2018, 128, 2104–2115. [Google Scholar] [CrossRef] [Green Version]
- Finn, R.S.; Qin, S.; Ikeda, M.; Galle, P.R.; Ducreux, M.; Kim, T.-Y.; Kudo, M.; Breder, V.; Merle, P.; Kaseb, A.O.; et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N. Engl. J. Med. 2020, 382, 1894–1905. [Google Scholar] [CrossRef] [PubMed]
- Huang, Y.; Yuan, J.; Righi, E.; Kamoun, W.S.; Ancukiewicz, M.; Nezivar, J.; Santosuosso, M.; Martin, J.D.; Martin, M.R.; Vianello, F.; et al. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc. Natl. Acad. Sci. USA 2012, 109, 17561–17566. [Google Scholar] [CrossRef] [Green Version]
- Rigamonti, N.; Kadioglu, E.; Keklikoglou, I.; Rmili, C.W.; Leow, C.C.; De Palma, M. Role of angiopoietin-2 in adaptive tumor resistance to VEGF signaling blockade. Cell Rep. 2014, 8, 696–706. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, X.; Giobbie-Hurder, A.; Liao, X.; Connelly, C.; Connolly, E.M.; Li, J.; Manos, M.P.; Lawrence, D.; McDermott, D.; Severgnini, M.; et al. Angiopoietin-2 as a biomarker and target for immune checkpoint therapy. Cancer Immunol. Res. 2017, 5, 17–28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dominguez, C.; McCampbell, K.K.; David, J.M.; Palena, C. Neutralization of IL-8 decreases tumor PMN-MDSCs and reduces mesenchymalization of claudin-low triple-negative breast cancer. JCI Insight 2017, 2. [Google Scholar] [CrossRef] [PubMed]
- Bilusic, M.; Heery, C.R.; Collins, J.M.; Donahue, R.N.; Palena, C.; Madan, R.A.; Karzai, F.; Marté, J.L.; Strauss, J.; Gatti-Mays, M.E.; et al. Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors. J. Immunother. Cancer 2019, 7, 240. [Google Scholar] [CrossRef] [PubMed]
- Siu, L.L.; Burris, H.; Le, D.T.; Hollebecque, A.; Steeghs, N.; Delord, J.P.; Hilton, J.; Barnhart, B.; Sega, E.; Sanghavi, K.; et al. Abstract CT180: Preliminary phase 1 profile of BMS-986179, an anti-CD73 antibody, in combination with nivolumab in patients with advanced solid tumors. Cancer Res. 2018, 78, 13. [Google Scholar] [CrossRef]
- El-Khoueiry, A.B.; Ning, Y.; Yang, D.; Cole, S.; Kahn, M.; Berg, M.Z.; Fujimori, M.; Inada, T.; Kouji, H.; Lenz, H.J. A phase I first-in-human study of PRI-724 in patients (pts) with advanced solid tumors. J. Clin. Oncol. 2013, 31, 2501. [Google Scholar] [CrossRef]
- Maurer, C.; Eiger, D.; Velghe, C.; Aftimos, P.; Maetens, M.; Gaye, J.; Paesmans, M.; Ignatiadis, M.; Piccart, M.; Buisseret, L. SYNERGY: Phase I and randomized phase II trial to investigate the addition of the anti-CD73 antibody oleclumab to durvalumab, paclitaxel and carboplatin for previously untreated, locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC). Ann. Oncol. 2019, 30, iii47–iii64. [Google Scholar] [CrossRef]
- Waugh, D.J.; Wilson, C. The interleukin-8 pathway in cancer. Clin. Cancer Res. 2008, 14, 6735–6741. [Google Scholar] [CrossRef] [Green Version]
- Liu, Q.; Li, A.; Tian, Y.; Wu, J.D.; Liu, Y.; Li, T.; Chen, Y.; Han, X.; Wu, K. The CXCL8-CXCR1/2 pathways in cancer. Cytokine Growth Factor Rev. 2016, 31, 61–71. [Google Scholar] [CrossRef] [Green Version]
- Kim, S.; You, D.; Jeong, Y.; Yu, J.; Kim, S.W.; Nam, S.J.; Lee, J.E. Berberine down-regulates IL-8 expression through inhibition of the EGFR/MEK/ERK pathway in triple-negative breast cancer cells. Phytomedicine 2018, 50, 43–49. [Google Scholar] [CrossRef] [PubMed]
- Cheng, Y.; Ma, X.-L.; Wei, Y.-Q.; Wei, X. Potential roles and targeted therapy of the CXCLs/CXCR2 axis in cancer and inflammatory diseases. Biochim. Biophys. Acta (BBA) Bioenergy 2019, 1871, 289–312. [Google Scholar] [CrossRef] [PubMed]
- Fernando, R.I.; Castillo, M.D.; Litzinger, M.; Hamilton, D.H.; Palena, C. IL-8 signaling plays a critical role in the epithelial-mesenchymal transition of human carcinoma cells. Cancer Res. 2011, 71, 5296–5306. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Acosta, J.C.; O’Loghlen, A.; Banito, A.; Guijarro, M.V.; Augert, A.; Raguz, S.; Fumagalli, M.; Da Costa, M.; Brown, C.; Popov, N.; et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 2008, 133, 1006–1018. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, A.; Dubey, S.; Varney, M.L.; Dave, B.J.; Singh, R.K. IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J. Immunol. 2003, 170, 3369–3376. [Google Scholar] [CrossRef] [PubMed]
- Shi, J.; Wei, P.-K. Interleukin-8: A potent promoter of angiogenesis in gastric cancer. Oncol. Lett. 2015, 11, 1043–1050. [Google Scholar] [CrossRef] [Green Version]
- Yu, J.; Du, W.; Yan, F.; Wang, Y.; Li, H.; Cao, S.; Yu, W.; Shen, C.; Liu, J.; Ren, X. Myeloid-derived suppressor cells suppress antitumor immune responses through IDO expression and correlate with lymph node metastasis in patients with breast cancer. J. Immunol. 2013, 190, 3783–3797. [Google Scholar] [CrossRef] [Green Version]
- Srivastava, M.K.; Sinha, P.; Clements, V.K.; Rodriguez, P.; Ostrand-Rosenberg, S. Myeloid-Derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res. 2010, 70, 68–77. [Google Scholar] [CrossRef] [Green Version]
- Nagaraj, S.; Gupta, K.; Pisarev, V.; Kinarsky, L.; Sherman, S.; Kang, L.; Herber, D.; Schneck, J.; Gabrilovich, D.I. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat. Med. 2007, 13, 828–835. [Google Scholar] [CrossRef] [Green Version]
- Molon, B.; Ugel, S.; Del Pozzo, F.; Soldani, C.; Zilio, S.; Avella, D.; De Palma, A.; Mauri, P.; Monegal, A.; Rescigno, M.; et al. Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. J. Exp. Med. 2011, 208, 1949–1962. [Google Scholar] [CrossRef] [PubMed]
- Highfill, S.L.; Cui, Y.; Giles, A.J.; Smith, J.P.; Zhang, H.; Morse, E.; Kaplan, R.N.; Mackall, C.L. Disruption of CXCR2-Mediated MDSC tumor trafficking enhances anti-PD1 efficacy. Sci. Transl. Med. 2014, 6, 237ra67. [Google Scholar] [CrossRef] [PubMed]
- Sanmamed, M.F.; Perez-Gracia, J.L.; Schalper, K.A.; Fusco, J.P.; Gonzalez, A.; Rodriguez-Ruiz, M.E.; Oñate, C.; Perez, G.; Alfaro, C.; Martín-Algarra, S.; et al. Changes in serum interleukin-8 (IL-8) levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small-cell lung cancer patients. Ann. Oncol. 2017, 28, 1988–1995. [Google Scholar] [CrossRef] [PubMed]
- Dallos, M.; Aggen, D.H.; Hawley, J.; Lim, E.A.; Stein, M.N.; Kelly, W.K.; Nanus, D.M.; Drake, C.G. A randomized phase Ib/II study of nivolumab with or without BMS-986253 in combination with a short course of ADT in men with castration-sensitive prostate cancer (MAGIC-8). J. Clin. Oncol. 2019, 37, TPS329. [Google Scholar] [CrossRef]
- Deaglio, S.; Dwyer, K.M.; Gao, W.; Friedman, D.; Usheva, A.; Erat, A.; Chen, J.F.; Enjyoji, K.; Linden, J.; Oukka, M.; et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med. 2007, 204, 1257–1265. [Google Scholar] [CrossRef] [Green Version]
- He, P.; Zhou, W.; Liu, M.; Chen, Y. Recent advances of small molecular regulators targeting G protein-coupled receptors family for oncology immunotherapy. Curr. Top. Med. Chem. 2019, 19, 1464–1483. [Google Scholar] [CrossRef]
- Sciarra, A.; Monteiro, I.; Ménétrier-Caux, C.; Caux, C.; Gilbert, B.; Halkic, N.; Rosa, S.L.; Romero, P.; Sempoux, C.; Leval, L.D. CD73 expression in normal and pathological human hepatobiliopancreatic tissues. Cancer Immunol. Immunother. 2019, 68, 467–478. [Google Scholar] [CrossRef] [Green Version]
- Jin, D.; Fan, J.; Wang, L.; Thompson, L.F.; Liu, A.; Daniel, B.J.; Shin, T.; Curiel, T.J.; Zhang, B. CD73 on Tumor cells impairs antitumor T-cell responses: A novel mechanism of tumor-induced immune suppression. Cancer Res. 2010, 70, 2245–2255. [Google Scholar] [CrossRef] [Green Version]
- Ryzhov, S.; Novitskiy, S.V.; Goldstein, A.E.; Biktasova, A.; Blackburn, M.R.; Biaggioni, I.; Dikov, M.M.; Foektistov, I. Adenosinergic regulation of the expansion and immunosuppressive activity of CD11b+Gr1+ cells. J. Immunol. 2011, 187, 6120–6129. [Google Scholar] [CrossRef] [Green Version]
- Synnestvedt, K.; Furuta, G.T.; Comerford, K.M.; Louis, N.; Karhausen, J.; Eltzschig, H.K.; Hansen, K.R.; Thompson, L.F.; Colgan, S.P. Ecto-5′-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J. Clin. Investig. 2002, 110, 993–1002. [Google Scholar] [CrossRef]
- Adzic, M.; Nedeljkovic, N. Unveiling the role of Ecto-5′-Nucleotidase/CD73 in astrocyte migration by using pharmacological tools. Front. Pharmacol. 2018, 9, 153. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takedachi, M.; Qu, D.; Ebisuno, Y.; Oohara, H.; Joachims, M.L.; McGee, S.T.; Maeda, E.; McEver, R.P.; Tanaka, T.; Miyasaka, M.; et al. CD73-generated adenosine restricts lymphocyte migration into draining lymph nodes. J. Immunol. 2008, 180, 6288–6296. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Loi, S.; Pommey, S.; Haibe-Kains, B.; Beavis, P.A.; Darcy, P.K.; Smyth, M.J.; Stagg, J. CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer. Proc. Natl. Acad. Sci. USA 2013, 110, 11091–11096. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kung, J.T.Y.; Colognori, D.; Lee, J.T. Long noncoding RNAs: Past, present, and future. Genetics 2013, 193, 651–669. [Google Scholar] [CrossRef] [Green Version]
- Wang, C.J.; Zhu, C.C.; Xu, J.; Wang, M.; Zhao, W.Y.; Liu, Q.; Zhao, G.; Zhang, Z.Z. The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs. Mol. Cancer 2019, 18, 115. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Campos-Parra, A.D.; López-Urrutia, E.; Moreno, L.T.O.; López-Camarillo, C.; Meza-Menchaca, T.; González, G.F.; Montes, L.P.B.; Pérez-Plasencia, C. Long non-coding RNAs as new master regulators of resistance to systemic treatments in breast cancer. Int. J. Mol. Sci. 2018, 19, 2711. [Google Scholar] [CrossRef] [Green Version]
- Yan, K.; Fu, Y.; Zhu, N.; Wang, Z.; Hong, J.-L.; Li, Y.; Li, W.-J.; Zhang, H.-B.; Song, J.-H. Repression of lncRNA NEAT1 enhances the antitumor activity of CD8+T cells against hepatocellular carcinoma via regulating miR-155/Tim-3. Int. J. Biochem. Cell Biol. 2019, 110, 1–8. [Google Scholar] [CrossRef]
- Xiping, Z.; Bo, C.; Shifeng, Y.; Feijiang, Y.; Hongjian, Y.; Qihui, C.; Binbin, T. Roles of MALAT1 in development and migration of triple negative and Her-2 positive breast cancer. Oncotarget 2018, 9, 2255–2267. [Google Scholar] [CrossRef] [Green Version]
- Wang, Q.-M.; Lian, G.-Y.; Song, Y.; Huang, Y.-F.; Gong, Y. LncRNA MALAT1 promotes tumorigenesis and immune escape of diffuse large B cell lymphoma by sponging miR-195. Life Sci. 2019, 231, 116335. [Google Scholar] [CrossRef]
- Lu, T.; Wang, Y.; Chen, D.; Liu, J.; Jiao, W. Potential clinical application of lncRNAs in non-small cell lung cancer. OncoTargets Ther. 2018, 11, 8045–8052. [Google Scholar] [CrossRef] [Green Version]
- Wu, T.; Du, Y. LncRNAs: From basic research to medical application. Int. J. Biol. Sci. 2017, 13, 295–307. [Google Scholar] [CrossRef] [PubMed]
- Cortes-Ciriano, I.; Lee, S.; Park, W.-Y.; Kim, T.-M.; Park, P.J. A molecular portrait of microsatellite instability across multiple cancers. Nat. Commun. 2017, 8, 15180. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Le, D.T.; Durham, J.N.; Smith, K.N.; Wang, H.; Barlett, B.R.; Aulakh, L.K.; Lu, S.; Kemberling, H.; Wilt, C.; Luber, B.S.; et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017, 357, 409–413. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Horimoto, Y.; Hlaing, M.T.; Saeki, H.; Kitano, S.; Nakai, K.; Sasaki, R.; Kurisaki-Arakawa, A.; Arakawa, A.; Otsuji, N.; Matsuoka, S.; et al. Microsatellite instability and mismatch repair protein expressions in lymphocyte-predominant breast cancer. Cancer Sci. 2020, 111, 2647–2654. [Google Scholar] [CrossRef] [PubMed]
- Hou, Y.; Nitta, H.; Parwani, A.V.; Li, Z. PD-L1 and CD8 are associated with deficient mismatch repair status in triple-negative and HER2-positive breast cancers. Hum. Pathol. 2019, 86, 108–114. [Google Scholar] [CrossRef] [PubMed]
- Mei, P.; Freitag, C.E.; Wei, L.; Zhang, Y.; Parwani, A.V.; Li, Z. High tumor mutation burden is associated with DNA damage repair gene mutation in breast carcinomas. Diagn. Pathol. 2020, 15, 1–7. [Google Scholar] [CrossRef]
- Zhu, Q.; Pao, G.M.; Huynh, A.M.; Suh, H.; Tonnu, N.; Nederlof, P.M.; Gage, F.H.; Verma, I.M. BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Nat. Cell Biol. 2011, 477, 179–184. [Google Scholar] [CrossRef]
- Nolan, E.; Savas, P.; Policheni, A.N.; Darcy, P.K.; Vaillant, F.; Mintoff, C.P.; Dushyanthen, S.; Mansour, M.; Pang, J.-M.B.; Fox, S.B.; et al. Combined immune checkpoint blockade as a therapeutic strategy forBRCA1-mutated breast cancer. Sci. Transl. Med. 2017, 9, eaal4922. [Google Scholar] [CrossRef]
- Le, D.T.; Uram, J.N.; Wang, H.; Bartlett, B.R.; Kemberling, H.; Eyring, A.D.; Skora, A.D.; Luber, B.S.; Azad, N.S.; Laheru, D.; et al. PD-1 Blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med. 2015, 372, 2509–2520. [Google Scholar] [CrossRef]
- Kahlert, U.D.; Maciaczyk, D.; Doostkam, S.; Orr, B.A.; Simons, B.; Bogiel, T.; Reithmeier, T.; Prinz, M.; Schubert, J.; Niedermann, G.; et al. Activation of canonical WNT/β-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition. Cancer Lett. 2012, 325, 42–53. [Google Scholar] [CrossRef]
- Vincan, E.; Barker, N. The upstream components of the Wnt signalling pathway in the dynamic EMT and MET associated with colorectal cancer progression. Clin. Exp. Metastasis 2008, 25, 657–663. [Google Scholar] [CrossRef] [PubMed]
- Loh, N.Y.; Hedditch, E.L.; Baker, A.L.; Jary, E.; Ward, R.L.; Ford, C.E. The Wnt signalling pathway is upregulated in an in vitro model of acquired tamoxifen resistant breast cancer. BMC Cancer 2013, 13, 174. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Green, J.L.; La, J.; Yum, K.W.; Desai, P.; Rodewald, L.-W.; Zhang, X.; Leblanc, M.; Nusse, R.; Lewis, M.T.; Wahl, G.M. Paracrine Wnt signaling both promotes and inhibits human breast tumor growth. Proc. Natl. Acad. Sci. USA 2013, 110, 6991–6996. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, J.; Prosperi, J.R.; Choudhury, N.; Olopade, O.I.; Goss, K.H. B-Catenin is required for the tumorigenic potential of triple-negative breast cancer cells. PLoS ONE 2015, 10, e0117097. [Google Scholar] [CrossRef] [Green Version]
- Pohl, S.-G.; Brook, N.; Agostino, M.; Arfuso, F.; Kumar, A.P.; Dharmarajan, A. Wnt signaling in triple-negative breast cancer. Oncogenesis 2017, 6, e310. [Google Scholar] [CrossRef] [Green Version]
- Spranger, S.; Bao, R.; Gajewski, T.F. Melanoma-intrinsic B-catenin signalling prevents anti-tumour immunity. Nat. Cell Biol. 2015, 523, 231–235. [Google Scholar] [CrossRef]
- De Galarreta, M.R.; Bresnahan, E.; Molina-Sánchez, P.; Lindblad, K.E.; Maier, B.; Sia, D.; Puigvehí, M.; Miguela, V.; Casanova-Acebes, M.; Dhainaut, M.; et al. B-Catenin activation promotes immune escape and resistance to Anti-PD-1 therapy in hepatocellular carcinoma. Cancer Discov. 2019, 9, 1124–1141. [Google Scholar] [CrossRef]
- Castagnoli, L.; Cancila, V.; Cordoba-Romero, S.L.; Faraci, S.; Talarico, G.; Belmonte, B.; Iorio, M.V.; Milani, M.; Volpari, T.; Chiodoni, C.; et al. WNT signaling modulates PD-L1 expression in the stem cell compartment of triple-negative breast cancer. Oncogene 2019, 38, 4047–4060. [Google Scholar] [CrossRef] [Green Version]
- Wang, B.; Tian, T.; Kalland, K.-H.; Ke, X.; Qu, Y. Targeting Wnt/B-Catenin signaling for cancer immunotherapy. Trends Pharmacol. Sci. 2018, 39, 648–658. [Google Scholar] [CrossRef]
- Driessens, G.; Zheng, Y.; Locke, F.; Cannon, J.L.; Gounari, F.; Gajewski, T.F. Beta-catenin inhibits T cell activation by selective interference with linker for activation of T cells-phospholipase C-y1phosphorylation. J. Immunol. 2010, 186, 784–790. [Google Scholar] [CrossRef]
- Kerdidani, D.; Chouvardas, P.; Arjo, A.R.; Giopanou, I.; Ntaliarda, G.; Guo, Y.A.; Tsikitis, M.; Kazamias, G.; Potaris, K.; Stathopoulos, G.T.; et al. Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma. Nat. Commun. 2019, 10, 1405. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bilir, B.; Kucuk, O.; Moreno, C.S. Wnt signaling blockage inhibits cell proliferation and migration, and induces apoptosis in triple-negative breast cancer cells. J. Transl. Med. 2013, 11, 280. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cordenonsi, M.; Zanconato, F.; Azzolin, L.; Forcato, M.; Rosato, A.; Frasson, C.; Inui, M.; Montagner, M.; Parenti, A.R.; Poletti, A.; et al. The hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell 2011, 147, 759–772. [Google Scholar] [CrossRef] [PubMed]
- Hiemer, S.E.; Szymaniak, A.D.; Varelas, X. The transcriptional regulators TAZ and YAP direct transforming growth factor &beta-induced tumorigenic phenotypes in breast cancer cells. J. Biol. Chem. 2014, 289, 13461–13474. [Google Scholar] [CrossRef] [Green Version]
- Chang, S.-S.; Yamaguchi, H.; Xia, W.; Lim, S.-O.; Khotskaya, Y.; Wu, Y.; Chang, W.-C.; Liu, Q.; Hung, M.-C. Aurora A kinase activates YAP signaling in triple-negative breast cancer. Oncogene 2017, 36, 1265–1275. [Google Scholar] [CrossRef] [PubMed]
- Azzolin, L.; Panciera, T.; Soligo, S.; Enzo, E.; Bicciato, S.; Dupont, S.; Bresolin, S.; Frasson, C.; Basso, G.; Guzzardo, V.; et al. YAP/TAZ incorporation in the B-Catenin destruction complex orchestrates the Wnt response. Cell 2014, 158, 157–170. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maeda, T.; Hiraki, M.; Jin, C.; Rajabi, H.; Tagde, A.; Alam, M.; Bouillez, A.; Hu, X.; Suzuki, Y.; Miyo, M.; et al. MUC1-C induces PD-L1 and immune evasion in triple-negative breast cancer. Cancer Res. 2017, 78, 205–215. [Google Scholar] [CrossRef] [Green Version]
- Kim, M.H.; Kim, C.G.; Kim, S.-K.; Shin, S.J.; Choe, E.A.; Park, S.H.; Shin, E.-C.; Kim, J. YAP-Induced PD-L1 expression drives immune evasion in BRAFi-Resistant melanoma. Cancer Immunol. Res. 2018, 6, 255–266. [Google Scholar] [CrossRef] [Green Version]
- Miao, J.; Hsu, P.-C.; Yang, Y.-L.; Xu, Z.; Dai, Y.; Wang, Y.; Chan, G.; Huang, Z.; Hu, B.; Li, H.; et al. YAP regulates PD-L1 expression in human NSCLC cells. Oncotarget 2017, 8, 114576–114587. [Google Scholar] [CrossRef] [Green Version]
- Wang, G.; Lu, X.; Dey, P.; Deng, P.; Wu, C.C.; Jiang, S.; Fang, Z.; Zhao, K.; Konaparthi, R.; Hua, S.; et al. Targeting YAP-Dependent MSDC infiltration impairs tumor progression. Cancer Discov. 2016, 6, 80–95. [Google Scholar] [CrossRef] [Green Version]
- Locati, M.; Mantovani, A.; Sica, A. Macrophage activation and polarization as an adaptive component of innate immunity. Adv. Immunol. 2013, 120, 163–184. [Google Scholar] [CrossRef] [PubMed]
- Yang, M.; Liu, J.; Shao, J.; Qin, Y.; Ji, Q.; Zhang, X.; Du, J. Cathepsin S-mediated autophagic flux in tumor-associated macrophages accelerate tumor development by promoting M2 polarization. Mol. Cancer 2014, 13, 43. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, W.; Yang, S.; Zhang, F.; Cheng, F.; Wang, X.; Rao, J. Influence of the Hippo-YAP signalling pathway on tumor associated macrophages (TAMs) and its implications on cancer immunosuppressive microenvironment. Ann. Transl. Med. 2020, 8, 399. [Google Scholar] [CrossRef] [PubMed]
- Nusse, R.; Clevers, H. Wnt/B-Catenin signaling, disease, and emerging therapeutic modalities. Cell 2017, 169, 985–999. [Google Scholar] [CrossRef] [PubMed]
- Ni, X.; Tao, J.; Barbi, J.; Chen, Q.; Park, B.V.; Li, Z.; Zhang, N.; Lebid, A.; Ramaswamy, A.; Wei, P.; et al. YAP is essential for treg-mediated suppression of antitumor immunity. Cancer Discov. 2018, 8, 1026–1043. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sulaiman, A.; McGarry, S.; Li, L.; Jia, D.; Ooi, S.; Addison, C.; Dimitroulakos, J.; Arnaout, A.; Nessim, C.; Yao, Z.; et al. Dual inhibition of Wnt and Yes-associated protein signaling retards the growth of triple-negative breast cancer in both mesenchymal and epithelial states. Mol. Oncol. 2018, 12, 423–440. [Google Scholar] [CrossRef]
- Saputra, E.C.; Huang, L.; Chen, Y.; Tucker-Kellogg, L. Combination therapy and the evolution of resistance: The theoretical merits of synergism and antagonism in cancer. Cancer Res. 2018, 78, 2419–2431. [Google Scholar] [CrossRef] [Green Version]
- Friedman, C.F.; Proverbs-Singh, T.A.; Postow, M.A. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: A review. JAMA Oncol. 2016, 2, 1346–1353. [Google Scholar] [CrossRef]
- Postow, M.A.; Sidlow, R.; Hellmann, M.D. Immune-Related adverse events associated with immune checkpoint blockade. N. Engl. J. Med. 2018, 378, 158–168. [Google Scholar] [CrossRef]
- Gurunathan, S.; Kang, M.-H.; Qasim, M.; Kim, J.-H. Nanoparticle-Mediated combination therapy: Two-in-one approach for cancer. Int. J. Mol. Sci. 2018, 19, 3264. [Google Scholar] [CrossRef] [Green Version]
- Shi, J.; Kantoff, P.W.; Wooster, R.; Farokhzad, O.C. Cancer nanomedicine: Progress, challenges, and opportunities. Nat. Rev. Cancer 2017, 17, 20–37. [Google Scholar] [CrossRef] [PubMed]
- Peer, D.; Karp, J.M.; Hong, S.; Farokhzad, O.C.; Margalit, R.; Langer, R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2007, 2, 751–760. [Google Scholar] [CrossRef] [PubMed]
- Sercombe, L.; Veerati, T.; Moheimani, F.; Wu, S.Y.; Sood, A.K.; Hua, S. Advances and challenges of liposome assisted drug delivery. Front. Pharmacol. 2015, 6, 286. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, J.; Chen, H.-J.; Hang, T.; Yu, T.; Liu, G.; He, G.; Xiao, S.; Yang, B.R.; Yang, C.; Liu, F.; et al. Physical activation of innate immunity by spiky particles. Nat. Nanotechnol. 2018, 13, 1078–1086. [Google Scholar] [CrossRef]
- Kuai, R.; Yuan, W.; Son, S.; Nam, J.; Xu, Y.; Fan, Y.; Schwendeman, A.; Moon, J.J. Elimination of established tumors with nanodisc-based combination chemoimmunotherapy. Sci. Adv. 2018, 4, eaao1736. [Google Scholar] [CrossRef]
- Roy, A.; Singh, M.S.; Upadhyay, P.; Bhaskar, S. Nanoparticle mediated co-delivery of paclitaxel and a TLR-4 agonist results in tumor regression and enhanced immune response in the tumor microenvironment of a mouse model. Int. J. Pharm. 2013, 445, 171–180. [Google Scholar] [CrossRef]
- He, C.; Duan, X.; Guo, N.; Chan, C.; Poon, C.; Weichselbaum, N.G.R.R.; Lin, W. Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy. Nat. Commun. 2016, 7, 12499. [Google Scholar] [CrossRef] [Green Version]
- Xu, C.; Yu, Y.; Sun, Y.; Kong, L.; Yang, C.; Hu, M.; Yang, T.; Zhang, J.; Hu, Q.; Zhang, Z. Transformable nanoparticle-enabled synergistic elicitation and promotion of immunogenic cell death for triple-negative breast cancer immunotherapy. Adv. Funct. Mater. 2019, 29, 1905213. [Google Scholar] [CrossRef]
- Wang, P.; Zhao, X.-H.; Wang, Z.; Meng, M.; Li, X.; Ning, Q. Generation 4 polyamidoamine dendrimers is a novel candidate of nano-carrier for gene delivery agents in breast cancer treatment. Cancer Lett. 2010, 298, 34–49. [Google Scholar] [CrossRef]
- Retif, P.; Pinel, S.; Toussaint, M.; Frochot, C.; Chouikrat, R.; Bastogne, T.; Barberi-Heyob, M. Nanoparticles for Radiation Therapy Enhancement: The Key Parameters. Theranostics 2015, 5, 1030–1044. [Google Scholar] [CrossRef] [Green Version]
- Ngwa, W.; Dougan, S.; Kumar, R. Combining nanoparticle-aided radiation therapy with immunotherapy to enhance local and metastatic tumor cell kill during pancreatic cancer treatment. Int. J. Radiat. Oncol. 2017, 99, E611–E612. [Google Scholar] [CrossRef]
- Ruiu, R.; Tarone, L.; Rolih, V.; Barutello, G.; Bolli, E.; Riccardo, F.; Cavallo, F.; Conti, L. Cancer stem cell immunology and immunotherapy: Harnessing the immune system against cancer’s source. Prog. Mol. Biol. Transl. Sci. 2019, 164, 119–188. [Google Scholar] [CrossRef] [PubMed]
- Yamada, R.; Takahashi, A.; Torigoe, T.; Morita, R.; Tamura, Y.; Tsukahara, T.; Kanaseki, T.; Kubo, T.; Watarai, K.; Kondo, T.; et al. Preferential expression of cancer/testis genes in cancer stem-like cells: Proposal of a novel sub-category, cancer/testis/stem gene. Tissue Antigens 2013, 81, 428–434. [Google Scholar] [CrossRef] [PubMed]
- Simpson, A.J.G.; Caballero, O.L.; Jungbluth, A.; Chen, Y.-T.; Old, L.J. Cancer/testis antigens, gametogenesis and cancer. Nat. Rev. Cancer 2005, 5, 615–625. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Li, J.; Wang, Y.; Zhang, Y.; Chu, J.; Sun, C.; Fu, Z.; Huang, Y.; Zhang, H.; Yuan, H.; et al. Roles of cancer/testis antigens (CTAs) in breast cancer. Cancer Lett. 2017, 399, 64–73. [Google Scholar] [CrossRef]
- Wei, X.; Chen, F.; Xin, K.; Wang, Q.; Yu, L.; Liu, B.; Liu, Q. Cancer-Testis antigen peptide vaccine for cancer immunotherapy: Progress and prospects. Transl. Oncol. 2019, 12, 733–738. [Google Scholar] [CrossRef]
- Li, Y.; Chu, J.; Li, J.; Feng, W.; Yang, F.; Wang, Y.; Zhang, Y.; Sun, C.; Yang, M.; Vasilatos, S.N.; et al. Cancer/testis antigen-Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway. Mol. Oncol. 2018, 12, 1233–1248. [Google Scholar] [CrossRef]
- Costanzo, V.; Bardelli, A.; Siena, S.; Abrignani, S. Exploring the links between cancer and placenta development. Open Biol. 2018, 8, 180081. [Google Scholar] [CrossRef] [Green Version]
- D’Souza, A.W.; Wagner, G.P. Malignant cancer and invasive placentation: A case for positive pleiotropy between endometrial and malignancy phenotypes. Evol. Med. Public Health 2014, 2014, 136–145. [Google Scholar] [CrossRef] [Green Version]
- Koslowski, M.; Sahin, U.; Mitnacht-Kraus, R.; Seitz, G.; Huber, C.; Türeci, Ö. A placenta-specific gene ectopically activated in many human cancers is essentially involved in malignant cell processes. Cancer Res. 2007, 67, 9528–9534. [Google Scholar] [CrossRef] [Green Version]
- Satie, A.-P.; Meyts, E.R.-D.; Spagnoli, G.C.; Henno, S.; Olivo, L.; Jacobsen, G.K.; Rioux-Leclercq, N.; Jégou, B.; Samson, M. The cancer-testis gene, NY-ESO-1, is expressed in normal fetal and adult testes and in spermatocytic seminomas and testicular carcinoma in situ. Lab. Investig. 2002, 82, 775–780. [Google Scholar] [CrossRef] [Green Version]
- Cronwright, G.; Blanc, K.L.; Götherström, C.; Darcy, P.; Ehnman, M.; Brodin, B. Cancer/testis antigen expression in human mesenchymal stem cells: Down-regulation of SSX impairs cell migration and matrix metalloproteinase 2 expression. Cancer Res. 2005, 65, 2207–2215. [Google Scholar] [CrossRef] [Green Version]
- Ademuyiwa, F.O.; Bshara, W.; Attwood, K.; Morrison, C.; Edge, S.B.; Karpf, A.R.; James, S.A.; Ambrosone, C.B.; O’Connor, T.L.; Levine, E.G.; et al. NY-ESO-1 cancer testis antigen demonstrates high immunogenicity in triple negative breast cancer. PLoS ONE 2012, 7, e38783. [Google Scholar] [CrossRef]
- Fourcade, J.; Kudela, P.; Sun, Z.; Shen, H.; Land, S.R.; Lenzner, D.; Guillaume, P.; Luescher, I.F.; Sander, C.; Ferrone, S.; et al. PD-1 is a regulator of NY-ESO-1-specific CD8+ T cell expansion in melanoma patients. J. Immunol. 2009, 182, 5240–5249. [Google Scholar] [CrossRef] [Green Version]
- Raghavendra, A.; Croft, P.K.; Vargas, A.C.; Smart, C.E.; Simpson, P.T.; Saunus, J.M.; Lakhani, S.R. Expression of MAGE-A and NY-ESO-1 cancer/testis antigens is enriched in triple-negative invasive breast cancers. Histopathology 2018, 73, 68–80. [Google Scholar] [CrossRef] [Green Version]
- Wang, X.; Qi, Y.; Kong, X.; Zhai, J.; Li, Y.; Song, Y.; Wang, J.; Feng, X.; Fang, Y. Immunological therapy: A novel thriving area for triple-negative breast cancer treatment. Cancer Lett. 2019, 442, 409–428. [Google Scholar] [CrossRef]
- Wang, H.; Sang, M.; Geng, C.; Liu, F.; Gu, L.; Shan, B. MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition. Neoplasma 2016, 63, 44–56. [Google Scholar] [CrossRef] [Green Version]
- Zajac, P.; Schultz-Thater, E.; Tornillo, L.; Sadowski, C.; Trella, E.; Mengus, C.; Iezzi, G.; Spagnoli, G.C. MAGE-A antigens and cancer immunotherapy. Front. Med. 2017, 4, 18. [Google Scholar] [CrossRef] [Green Version]
- Vansteenkiste, J.; Cho, B.C.; Vanakesa, T.; De Pas, T.; Zielinski, M.; Kim, M.S.; Jassem, J.; Yoshimura, M.; Dahabreh, J.; Nakayama, H.; et al. Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016, 17, 822–835. [Google Scholar] [CrossRef]
- Thomas, R.; Al-Khadairi, G.; Roelands, J.; Hendrickx, W.; Dermime, S.; Bedognetti, D.; Decock, J. NY-ESO-1 based immunotherapy of cancer: Current perspectives. Front. Immunol. 2018, 9, 947. [Google Scholar] [CrossRef]
- Chomez, P.; De Backer, O.; Bertrand, M.; De Plaen, E.; Boon, T.; Lucas, S. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 2001, 61, 5544–5551. [Google Scholar] [PubMed]
- Fennemann, F.L.; De Vries, I.J.M.; Figdor, C.G.; Verdoes, M. Attacking tumors from all sides: Personalized multiplex vaccines to tackle intratumor heterogeneity. Front. Immunol. 2019, 10, 824. [Google Scholar] [CrossRef] [PubMed]
- Ning, N.; Pan, Q.; Zheng, F.; Teitz-Tennenbaum, S.; Egenti, M.; Yet, J.; Li, M.; Ginestier, C.; Wicha, M.S.; Moyer, J.S.; et al. Cancer stem cell vaccination confers significant antitumor immunity. Cancer Res. 2012, 72, 1853–1864. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Constantino, J.; Gomes, C.; Falcão, A.; Neves, B.M.; Cruz, M.T. Dendritic cell-based immunotherapy: A basic review and recent advances. Immunol. Res. 2017, 65, 798–810. [Google Scholar] [CrossRef] [PubMed]
- Boudreau, J.E.; Bonehill, A.; Thielemans, K.; Wan, Y. Engineering dendritic cells to enhance cancer immunotherapy. Mol. Ther. 2011, 19, 841–853. [Google Scholar] [CrossRef] [Green Version]
- Tagliamonte, M.; Petrizzo, A.; Tornesello, M.L.; Buonaguro, F.M.; Buonaguro, L. Antigen-specific vaccines for cancer treatment. Hum. Vaccines Immunother. 2014, 10, 3332–3346. [Google Scholar] [CrossRef]
- Stanton, S.E.; Gad, E.; Corulli, L.R.; Lu, H.; Disis, M.L. Tumor-associated antigens identified early in mouse mammary tumor development can be effective vaccine targets. Vaccine 2019, 37, 3552–3561. [Google Scholar] [CrossRef]
- Jarnicki, A.G.; Conroy, H.; Brereton, C.; Donnelly, G.; Toomey, D.; Walsh, K.; Sweeney, C.; Leavy, O.; Fletcher, J.; Lavelle, E.C.; et al. Attenuating regulatory T cell induction by TLR agonists through inhibition of p38 MAPK signaling in dendritic cells enhances their efficacy as vaccine adjuvants and cancer immunotherapeutics. J. Immunol. 2008, 180, 3797–3806. [Google Scholar] [CrossRef] [Green Version]
- Goutagny, N.; Estornes, Y.; Hasan, U.; Lebecque, S.; Caux, C. Targeting pattern recognition receptors in cancer immunotherapy. Target. Oncol. 2012, 7, 29–54. [Google Scholar] [CrossRef]
- Wölfle, S.J.; Strebovsky, J.; Bartz, H.; Sähr, A.; Arnold, C.; Kaiser, C.; Dalpke, A.H.; Heeg, K. PD-L1 expression n tolerogenic APCs is controlled by STAT-3. Eur. J. Immunol. 2011, 41, 413–424. [Google Scholar] [CrossRef]
- Fend, L.; Yamazaki, T.; Remy, C.; Fahrner, C.; Gantzer, M.; Nourtier, V.; Préville, X.; Quéméneur, E.; Kepp, O.; Adam, J.; et al. Immune checkpoint blockade, immunogenic chemotherapy or IFN-ɑ blockade boost the local and abscopal effects of oncolytic virotherapy. Cancer Res. 2017, 77, 4146–4157. [Google Scholar] [CrossRef] [Green Version]
- Lichty, B.D.; Breitbach, C.J.; Stojdl, D.F.; Bell, J.C. Going viral with cancer immunotherapy. Nat. Rev. Cancer 2014, 14, 559–567. [Google Scholar] [CrossRef] [PubMed]
- Qureshy, Z.; Johnson, D.E.; Grandis, J.R. Targeting the JAK/STAT pathway in solid tumors. J. Cancer Metastasis Treat. 2020, 6, 27. [Google Scholar] [CrossRef]
- Marelli, G.; Howells, A.; Lemoine, N.R.; Wang, Y. Oncolytic viral therapy and the immune system: A double-edged sword against cancer. Front. Immunol. 2018, 9, 866. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Felt, S.A.; Moerdyk-Schauwecker, M.J.; Grdzelishvili, V.Z. Induction of apoptosis in pancreatic cancer cells by vesicular stomatitis virus. Virology 2015, 474, 163–173. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kanerva, A.; Nokisalmi, P.; Diaconu, I.; Koski, A.; Cerullo, V.; Liikanen, I.; Tähtinen, S.; Oksanen, M.; Heiskanen, R.; Pesonen, S.; et al. Antiviral and antitumor T-cell immunity in patients treated with GM-CSF-coding oncolytic adenovirus. Clin. Cancer Res. 2013, 19, 2734–2744. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Angelova, A.L.; Grekova, S.P.; Heller, A.; Kuhlmann, O.; Soyka, E.; Giese, T.; Aprahamian, M.; Bour, G.; Rüffer, S.; Cziepluch, C.; et al. Complementary induction of immunogenic cell death by oncolytic parvovirus H-1PV and gemcitabine in pancreatic cancer. J. Virol. 2014, 88, 5263–5276. [Google Scholar] [CrossRef] [Green Version]
- Shi, T.; Song, X.; Wang, Y.; Liu, F.; Wei, J. Combining oncolytic viruses with cancer immunotherapy: Establishing a new generation of cancer treatment. Front. Immunol. 2020, 11, 683. [Google Scholar] [CrossRef]
- Ribas, A.; Dummer, R.; Puzanov, I.; VanderWalde, A.; Andtbacka, R.H.I.; Michielin, O.; Olszanski, A.J.; Malvehy, J.; Cebon, J.; Fernandez, E.; et al. Oncolytic virotherapy promotes intratumoral T cell infiltration and improves Anti-PD-1 immunotherapy. Cell 2017, 170, 1109–1119. [Google Scholar] [CrossRef] [Green Version]
- Soliman, H.; Hogue, D.; Han, H.; Mooney, B.; Costa, R.; Lee, M.C.; Niell, B.; Khakapour, N.; Weinfurtner, R.J.; Hoover, S.; et al. Abstract CT040: A phase I trial of talimogene laherparepvec combined with neoadjuvant chemotherapy for non-metastatic triple negative breast cancer. Clinical Trials 2019, 79, CT040. [Google Scholar] [CrossRef]
- Woller, N.; Knocke, S.; Mundt, B.; Gürlevik, E.; Strüver, N.; Kloos, A.; Boozari, B.; Schache, P.; Manns, M.P.; Malek, N.P.; et al. Virus-induced tumor inflammation facilitates effective DC cancer immunotherapy in a Treg-dependent manner in mice. J. Clin. Investig. 2011, 121, 2570–2582. [Google Scholar] [CrossRef] [PubMed]
- Pol, J.G.; Acuna, S.A.; Yadollahi, B.; Tang, N.; Stephenson, K.B.; Atherton, M.J.; Hanwell, D.; El-Warrak, A.; Goldstein, A.; Moloo, B.; et al. Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials. OncoImmunology 2019, 8, e1512329. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Singh, N.; June, C.H. Boosting engineered T cells. Science 2019, 365, 119–120. [Google Scholar] [CrossRef] [PubMed]
- Ma, L.; Dichwalkar, T.; Chang, J.Y.; Cossette, B.; Garafola, D.; Zhang, A.Q.; Fichter, M.; Wang, C.; Liang, S.; Silva, M.; et al. Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor. Science 2019, 365, 162–168. [Google Scholar]
- Giavridis, T.; Stegen, S.J.C.V.D.; Eyquem, J.; Hamieh, M.; Piersigilli, A.; Sadelain, M. CAR T cell-induced cytokine release syndrome is mediated by macrophages and ablated by IL-1 blockade. Nat. Med. 2018, 24, 731–738. [Google Scholar] [CrossRef]
- Zhou, R.; Yazdanifar, M.; Das Roy, L.; Whilding, L.M.; Gavrill, A.; Maher, J.; Mukherjee, P. CAR T cells targeting the tumor MUC1 glycoprotein reduce triple-negative breast cancer growth. Front. Immunol. 2019, 10, 1149. [Google Scholar] [CrossRef] [Green Version]
- Byrd, T.T.; Fousek, K.; Pignata, A.; Szot, C.; Samaha, H.; Seaman, S.; Dobrolecki, L.; Salsman, V.S.; Oo, H.Z.; Bielamowicz, K.; et al. TEM8/ANTXR1-Specific CAR T cells as a targeted therapy for triple-negative breast cancer. Cancer Res. 2018, 78, 489–500. [Google Scholar] [CrossRef] [Green Version]
- Zhao, X.; Qu, J.; Hui, Y.; Zhang, H.; Sun, Y.; Liu, X.; Zhao, X.; Zhao, Z.; Yang, Q.; Wang, F.; et al. Clinicopathological and prognostic significance of c-Met overexpression in breast cancer. Oncotarget 2017, 8, 56758–56767. [Google Scholar] [CrossRef] [Green Version]
- Tchou, J.; Zhao, Y.; Levine, B.L.; Zhang, P.J.; Davis, M.M.; Melenhorst, J.J.; Kulikovskaya, I.; Brennan, A.L.; Liu, X.; Lacey, S.F.; et al. Safety and efficacy of intratumoral injections of chimeric antigen receptor (CAR) T cells in metastatic breast cancer. Cancer Immunol. Res. 2017, 5, 1152–1161. [Google Scholar] [CrossRef] [Green Version]
- Han, Y.; Xie, W.; Song, D.-G.; Powell, D.J., Jr. Control of triple-negative breast cancer using ex vivo self-enriched, costimulated NKG2D CAR T cells. J. Hematol. Oncol. 2018, 11, 92. [Google Scholar] [CrossRef]
- Abdel-Latif, M.; Youness, R.A. Why natural killer cells in triple negative breast cancer? World J. Clin. Oncol. 2020, 11, 464–476. [Google Scholar] [CrossRef] [PubMed]
- Dupuy, F.; Tabariès, S.; Andrzejewski, S.; Dong, Z.; Blagih, J.; Annis, M.G.; Omeroglu, A.; Gao, D.; Leung, S.; Amir, E.; et al. PDK1-Dependent metabolic reprogramming dictates metastatic potential in breast cancer. Cell Metab. 2015, 22, 577–589. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vanhove, K.; Graulus, G.-J.; Mesotten, L.; Thomeer, M.; Derveaux, E.; Noben, J.-P.; Guedens, W.; Adriaensens, P. The metabolic landscape of lung cancer: New insights in a disturbed glucose metabolism. Front. Oncol. 2019, 9, 1215. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lanning, N.J.; Castle, J.P.; Singh, S.J.; Leon, A.N.; Tovar, E.A.; Sanghera, A.; MacKeigan, J.P.; Filipp, F.V.; Graveel, C.R. Metabolic profiling of triple-negative breast cancer cells reveals metabolic vulnerabilities. Cancer Metab. 2017, 5, 6. [Google Scholar] [CrossRef] [PubMed]
- Choi, J.; Jung, W.-H.; Koo, J.S. Metabolism-Related proteins are differentially expressed according to the molecular subtype of invasive breast cancer defined by surrogate immunohistochemistry. Pathobiology 2013, 80, 41–52. [Google Scholar] [CrossRef]
- Romero-Cordoba, S.L.; Rodriguez-Cuevas, S.; Bautista-Pina, V.; Maffuz-Aziz, A.; D’Ippolito, E.; Cosentino, G.; Baroni, S.; Iorio, M.V.; Hidalgo-Miranda, A. Loss of function of miR-342-3p results in MCT1 over-expression and contributes to oncogenic metabolic reprogramming in triple negative breast cancer. Sci. Rep. 2018, 8, 12252. [Google Scholar] [CrossRef]
- Avanzato, D.; Pupo, E.; Ducano, N.; Isella, C.; Bertalot, G.; Luise, C.; Pece, S.; Bruna, A.; Rueda, O.M.; Caldas, C.; et al. High USP6NL levels in breast cancer sustain chronic AKT phosphorylation and GLUT1 stability fueling aerobic glycolysis. Cancer Res. 2018, 78, 3432–3444. [Google Scholar] [CrossRef] [Green Version]
- Ma, T.; Liu, H.; Liu, Y.; Liu, T.; Wang, H.; Qiao, F.; Song, L.; Zhang, L. USP6NL mediated by LINC00689/miR-142-3p promotes the development of triple-negative breast cancer. BMC Cancer 2020, 20, 998. [Google Scholar] [CrossRef]
- Shen, L.; O’Shea, J.M.; Kaadige, M.R.; Cunha, S.; Wilde, B.R.; Cohen, A.L.; Welm, A.L.; Ayer, D.E. Metabolic reprogramming in triple-negative breast cancer through Myc suppression of TXNIP. Proc. Natl. Acad. Sci. USA 2018, 112, 5425–5430. [Google Scholar] [CrossRef] [Green Version]
- Park, J.H.; Vithayathil, S.; Kumar, S.; Sung, P.-L.; Dobrolecki, L.E.; Putluri, V.; Bhat, V.B.; Bhowmik, S.K.; Gupta, V.; Arora, K.; et al. Fatty acid oxidation-driven Src links mitochondrial energy reprogramming and oncogenic properties in triple-negative breast cancer. Cell Rep. 2016, 14, 2154–2165. [Google Scholar] [CrossRef] [Green Version]
- Bellone, M.; Calcinotto, A.; Filipazzi, P.; De Milito, A.; Fais, S.; Rivoltini, L. The acidity of the tumor microenvironment is a mechanism of immune escape that can be overcome by proton pump inhibitors. OncoImmunology 2013, 2, e22058. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Díaz, F.E.; Dantas, E.; Geffner, J. Unravelling the interplay between extracellular acidosis and immune cells. Mediat. Inflamm. 2018, 2018, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Huang, X.; Xie, X.; Wang, H.; Xiao, X.; Yang, L.; Tian, Z.; Guo, X.; Zhang, L.; Tang, H.; Xie, X. PDL1 and LDHA act as ceRNAs in triple negative breast cancer by regulating miR-34a. J. Exp. Clin. Cancer Res. 2017, 36, 129. [Google Scholar] [CrossRef] [Green Version]
- Feng, J.; Yang, H.; Zhang, Y.; Wei, H.; Zhu, Z.; Zhu, B.; Yang, M.; Cao, W.; Wang, L.; Wu, Z. Tumor cell-derived lactate induces TAZ-dependent upregulation of PD-L1 through GPR81 in human lung cancer cells. Oncogene 2017, 36, 5829–5839. [Google Scholar] [CrossRef] [PubMed]
- Sprowl-Tanio, S.; Habowski, A.N.; Pate, K.T.; McQuade, M.M.; Wang, K.; Edwards, R.A.; Grun, F.; Lyou, Y.; Waterman, M.L. Lactate/pyruvate transporter MCT-1 is a direct Wnt target that confers sensitivity to 3-bromopyruvate in colon cancer. Cancer Metab. 2016, 4, 20. [Google Scholar] [CrossRef] [Green Version]
- Van Geldermalsen, M.; Wang, Q.; Nagarajah, R.; Marshall, A.D.; Thoeng, A.; Gao, D.; Ritchie, W.; Feng, Y.; Bailey, C.G.; Deng, N.; et al. ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer. Oncogene 2016, 35, 3201–3208. [Google Scholar] [CrossRef] [Green Version]
- Lampa, M.; Arlt, H.; Christopher, W.; Ospina, B.; Reeves, J.; Zhang, B.; Murtie, J.; Deng, G.; Barberis, C.; Hoffmann, D.; et al. Glutaminase is essential for the growth of triple-negative breast cancer cells with a deregulated glutamine metabolism pathway and its suppression synergizes with mTOR inhibition. PLoS ONE 2017, 12, e0185092. [Google Scholar] [CrossRef]
- Leone, R.D.; Zhao, L.; Englert, J.M.; Sun, I.-M.; Oh, M.-H.; Arwood, M.L.; Bettencourt, I.A.; Patel, C.H.; Wen, J.; Tam, A.; et al. Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Science 2019, 366, 1013–1021. [Google Scholar] [CrossRef]
- Ogrodzinski, M.P.; Bernard, J.J.; Lunt, S.Y. Deciphering metabolic rewiring in breast cancer subtypes. Transl. Res. 2017, 189, 105–122. [Google Scholar] [CrossRef]
- Han, S.; Wei, R.; Zhang, X.; Jiang, N.; Fan, M.; Huang, J.H.; Xie, B.; Zhang, L.; Miao, W.; Butler, A.C.-P.; et al. CPT1A/2-Mediated FAO enhancement—A metabolic target in radioresistant breast cancer. Front. Oncol. 2019, 9, 1201. [Google Scholar] [CrossRef]
- Wang, T.; Fahrmann, J.F.; Lee, H.; Li, Y.J.; Tripathi, S.C.; Yue, C.; Zhang, C.; Lifshitz, V.; Song, J.; Yuan, Y.; et al. JAK/STAT3-Regulated fatty acid β-oxidation is critical for breast cancer stem cell self-renewal and chemoresistance. Cell Metab. 2018, 27, 136–150. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Casciano, J.C.; Perry, C.; Cohen-Nowak, A.J.; Miller, K.D.; Voorde, J.V.; Zhang, Q.; Chalmers, S.; Sandison, M.E.; Liu, Q.; Hedley, A.; et al. MYC regulates fatty acid metabolism through a multigenic program in claudin-low triple negative breast cancer. Br. J. Cancer 2020, 122, 868–884. [Google Scholar] [CrossRef] [PubMed]
- Miska, J.; Lee-Chang, C.; Rashidi, A.; Muroski, M.E.; Chang, A.L.; Lopez-Rosas, A.; Zhang, P.; Panek, W.K.; Cordero, A.; Han, Y.; et al. HIF-1α is a metabolic switch between glycolytic-driven migration and oxidative phosphorylation-driven immunosuppression of Tregs in Glioblastoma. Cell Rep. 2019, 27, 226–237.e4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, T.; Stewart, K.M.; Wang, X.; Liu, K.; Xie, M.; Ryu, J.K.; Li, K.; Ma, T.; Wang, H.; Ni, L.; et al. Metabolic control of Th17 and induced Treg cell balance by an epigenetic mechanism. Nature 2017, 548, 228–233. [Google Scholar] [CrossRef]
- Camarda, R.; Zhou, A.Y.; Kohnz, R.A.; Balakrishnan, S.; Mahieu, C.; Anderton, B.; Eyob, H.; Kajimura, S.; Tward, A.; Krings, G.; et al. Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer. Nat. Med. 2016, 22, 427–432. [Google Scholar] [CrossRef]
- Kuzu, O.F.; Noory, M.A.; Robertson, G.P. The role of cholesterol in cancer. Cancer Res. 2018, 76, 2063–2070. [Google Scholar] [CrossRef] [Green Version]
- Szlasa, W.; Zendran, I.; ZalesiŃska, A.; Tarek, M.; Kulbacka, J. Lipid composition of the cancer cell membrane. J. Bioenerg. Biomembr. 2020, 52, 321–342. [Google Scholar] [CrossRef]
- Ehmsen, S.; Pedersen, M.H.; Wang, G.; Terp, M.G.; Arslanagic, A.; Hood, B.L.; Conrads, T.P.; Leth-Larsen, R.; Ditzel, H.J. Increased cholesterol biosynthesis is a key characteristic of breast cancer stem cells influencing patient outcome. Cell Rep. 2019, 27, 3927–3938.e6. [Google Scholar] [CrossRef] [Green Version]
- Cai, D.; Zhang, X.; Chen, H.-W. A master regulator of cholesterol biosynthesis constitutes a therapeutic liability of triple negative breast cancer. Mol. Cell. Oncol. 2020, 7, 1701362. [Google Scholar] [CrossRef]
- Shaitelman, S.F.; Stauder, M.C.; Allen, P.; Reddy, S.; Lakoski, S.; Atkinson, B.; Reddy, J.P.; Amaya, D.; Guerra, W.; Ueno, N.; et al. Impact of statin use on outcomes in triple negative breast cancer. J. Cancer 2017, 8, 2026–2032. [Google Scholar] [CrossRef] [Green Version]
- Sorrentino, G.; Ruggeri, N.; Specchia, V.; Cordenonsi, M.; Mano, M.; Dupont, S.; Manfrin, A.; Ingallina, E.; Sommaggio, R.; Piazza, S.; et al. Metabolic control of YAP and TAZ by the mevalonate pathway. Nat. Cell Biol. 2014, 16, 357–366. [Google Scholar] [CrossRef] [PubMed]
- Momtazi-Borojeni, A.A.; Nik, M.E.; Jaafari, M.R.; Banach, M.; Sahebkar, A. Effects of immunization against PCSK9 in an experimental model of breast cancer. Arch. Med. Sci. 2019, 15, 570–579. [Google Scholar] [CrossRef] [PubMed]
- Bietz, A.; Zhu, H.; Xue, M.; Xu, C. Cholesterol metabolism in T Cells. Front. Immunol. 2017, 8, 1664. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ma, X.; Bi, E.; Lu, Y.; Su, P.; Huang, C.; Liu, L.; Wang, Q.; Yang, M.; Kalady, M.F.; Qian, J.; et al. Cholesterol induces CD8+ T cell exhaustion in the tumor microenvironment. Cell Metab. 2019, 30, 143–156.e5. [Google Scholar] [CrossRef]
- Bharti, S.K.; Mironchik, Y.; Wildes, F.; Penet, M.-F.; Goggins, E.; Krishnamachary, B.; Bhujwalla, Z.M. Metabolic consequences of HIF silencing in a triple negative human breast cancer xenograft. Oncotarget 2018, 9, 15326–15339. [Google Scholar] [CrossRef]
- Pérez-Hernández, M.; Arias, A.; Martínez-García, D.; Pérez-Tomás, R.; Quesada, R.; Soto-Cerrato, V. Targeting autophagy for cancer treatment and tumor chemosensitization. Cancers 2019, 11, 1599. [Google Scholar] [CrossRef] [Green Version]
- Zhao, H.; Yang, M.; Zhao, J.; Wang, J.; Zhang, Y.; Zhang, Q. High expression of LC3B is associated with progression and poor outcome in triple-negative breast cancer. Med. Oncol. 2013, 30, 475. [Google Scholar] [CrossRef]
- Zhang, Q.; Zhang, Y.; Zhang, P.; Chao, Z.; Xia, F.; Jiang, C.C.; Zhang, X.D.; Jiang, Z.; Liu, H. Hexokinase II inhibitor, 3-BrPA induced autophagy by stimulating ROS formation in human breast cancer cells. Genes Cancer 2014, 5, 100–112. [Google Scholar] [CrossRef] [Green Version]
- Li, M.; Liu, J.; Li, S.; Feng, Y.; Yi, F.; Wang, L.; Wei, S.; Cao, L. Autophagy-related 7 modulates tumor progression in triple-negative breast cancer. Lab. Investig. 2019, 99, 1266–1274. [Google Scholar] [CrossRef]
- Qiao, Z.; Li, X.; Kang, N.; Yang, Y.; Chen, C.; Wu, T.; Zhao, M.; Liu, Y.; Ji, X. A novel specific Anti-CD73 antibody inhibits triple-negative breast cancer cell motility by regulating autophagy. Int. J. Mol. Sci. 2019, 20, 1057. [Google Scholar] [CrossRef] [Green Version]
- Wen, J.; Yeo, S.; Wang, C.; Chen, S.; Sun, S.; Haas, M.A.; Tu, W.; Jin, F.; Guan, J.-L. Autophagy inhibition re-sensitizes pulse stimulation-selected paclitaxel-resistant triple negative breast cancer cells to chemotherapy-induced apoptosis. Breast Cancer Res. Treat. 2015, 149, 619–629. [Google Scholar] [CrossRef] [Green Version]
- Halama, A.; Kulinski, M.; Dib, S.S.; Zaghlool, S.B.; Siveen, K.S.; Iskandarani, A.; Zierer, J.; Prabhu, K.S.; Satheesh, N.J.; Bhagwat, A.M.; et al. Accelerated lipid catabolism and autophagy are cancer survival mechanisms under inhibited glutaminolysis. Cancer Lett. 2018, 430, 133–147. [Google Scholar] [CrossRef] [PubMed]
- Bosc, C.; Broin, N.; Fanjul, M.; Saland, E.; Farge, T.; Courdy, C.; Batut, A.; Masoud, R.; Larrue, C.; Skuli, S.; et al. Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites. Nat. Commun. 2020, 11, 4056. [Google Scholar] [CrossRef] [PubMed]
- Li, Z.-L.; Zhang, H.-L.; Huang, Y.; Huang, J.-H.; Sun, P.; Zhou, N.-N.; Chen, Y.-H.; Mai, J.; Wang, Y.; Yu, Y.; et al. Autophagy deficiency promotes triple-negative breast cancer resistance to T cell-mediated cytotoxicity by blocking tenascin-C degradation. Nat. Commun. 2020, 11, 3806. [Google Scholar] [CrossRef] [PubMed]
- Du, Y.; Wei, N.; Ma, R.; Jiang, S.; Song, D. A miR-210-3p regulon that controls the warburg effect by modulating HIF-1α and p53 activity in triple-negative breast cancer. Cell Death Dis. 2020, 11, 731. [Google Scholar] [CrossRef]
- Lee, S.; Hallis, S.P.; Jung, K.-A.; Ryu, D.; Kwak, M.-K. Impairment of HIF-1α-mediated metabolic adaption by NRF2-silencing in breast cancer cells. Redox Biol. 2019, 24, 101210. [Google Scholar] [CrossRef] [PubMed]
- Lan, J.; Lu, H.; Samanta, D.; Salman, S.; Lu, Y.; Semenza, G.L. Hypoxia-inducible factor 1-dependent expression of adenosine receptor 2B promotes breast cancer stem cell enrichment. Proc. Natl. Acad. Sci. USA 2018, 115, E9640–E9648. [Google Scholar] [CrossRef] [Green Version]
- Zhang, H.; Lu, H.; Xiang, L.; Bullen, J.W.; Zhang, C.; Samanta, D.; Gilkes, D.M.; He, J.; Semenza, G.L. HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells. Proc. Natl. Acad. Sci. USA 2015, 112, E6215–E6223. [Google Scholar] [CrossRef] [Green Version]
- Liu, X.; Kwon, H.; Li, Z.; Fu, Y.-X. Is CD47 an innate immune checkpoint for tumor evasion? J. Hematol. Oncol. 2017, 10, 12. [Google Scholar] [CrossRef] [Green Version]
- Yuan, J.; Shi, X.; Chen, C.; He, H.; Liu, L.; Wu, J.; Yan, H. High expression of CD47 in triple negative breast cancer is associated with epithelial-mesenchymal transition and poor prognosis. Oncol. Lett. 2019, 18, 3249–3255. [Google Scholar] [CrossRef] [Green Version]
- Zhang, W.; Huang, Q.; Xiao, W.; Zhao, Y.; Pi, J.; Xu, H.; Zhao, H.; Xu, J.; Evans, C.; Jin, H. Advances in anti-tumor treatments targeting the CD47/SIRPα axis. Front. Immunol. 2020, 11, 18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gu, S.; Ni, T.; Wang, J.; Liu, Y.; Fan, Q.; Wang, Y.; Huang, T.; Chu, Y.; Sun, X.; Wang, Y. CD47 blockade inhibits tumor progression through promoting phagocytosis of tumor cells by M2 polarized macrophages in endometrial cancer. J. Immunol. Res. 2018, 2018, 6156757. [Google Scholar] [CrossRef] [PubMed]
- Ingram, J.R.; Blomberg, O.S.; Sockolosky, J.T.; Ali, L.; Schmidt, F.I.; Pishesha, N.; Espinosa, C.; Dougan, S.K.; Garcia, K.C.; Ploegh, H.L.; et al. Localized CD47 blockade enhances immunotherapy for murine melanoma. Proc. Natl. Acad. Sci. USA 2017, 114, 10184–10189. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kaur, S.; Elkahloun, A.G.; Singh, S.P.; Chen, Q.-R.; Meerzaman, D.M.; Song, T.; Manu, N.; Wu, W.; Mannan, P.; Garfield, S.H.; et al. A function-blocking CD47 antibody suppresses stem cell and EGF signaling in triple-negative breast cancer. Oncotarget 2016, 7, 10133–10152. [Google Scholar] [CrossRef]
- Sikic, B.I.; Lakhani, N.; Patnaik, A.; Shah, S.A.; Chandana, S.R.; Rasco, D.; Colevas, A.D.; O’Rourke, T.; Narayanan, S.; Papadopoulos, K.; et al. First-in-Human, first-in-class phase I trial of the anti-CD47 antibody Hu5F9-G4 in patients with advanced cancers. J. Clin. Oncol. 2019, 37, 946–953. [Google Scholar] [CrossRef]
- Hu, T.; Liu, H.; Liang, Z.; Wang, F.; Zhou, C.; Zheng, X.; Zhang, Y.; Song, Y.; Hu, J.; He, X.; et al. Tumor-intrinsic CD47 signal regulates glycolysis and promotes colorectal cancer cell growth and metastasis. Theranostics 2020, 10, 4056–4072. [Google Scholar] [CrossRef]
- Noman, M.Z.; DeSantis, G.; Janji, B.; Hasmim, M.; Karray, S.; Dessen, P.; Bronte, V.; Chouaib, S. PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J. Exp. Med. 2014, 211, 781–790. [Google Scholar] [CrossRef]
Trial (National Clinical Trial Identifier) | Phase | Condition | Interventions | Key Results | Reference |
---|---|---|---|---|---|
Atezolizumab Monotherapy (NCT01375842) | I | Locally advanced or metastatic solid tumors |
| Median PFS: 4.0 months for arm (1); 1.8 months for arm (2) Median OS: 17.6 months for arm (1); 7.3 months for arm (2) Incidence of trAEs: 62% for arm (1); 43% for arm (2) | [23] |
IMpassion130 (NCT02425891) | III | Previously untreated metastatic TNBC |
| Median PFS: 7.2 months for arm (1); 5.5 months for arm (2) Median OS: 21.3 months for arm (1); 17.6 months for arm (2) Incidence of grade 3+ trAEs: 15.9% for arm (1); 8.2% for arm (2) | [24] |
KEYNOTE-086 (NCT02447003) | II | Metastatic TNBC |
| Median PFS: 2.0 months for previously treated; 2.1 months for PD-L1+ tumors Median OS: 9.0 months for previously treated; 18.0 months for PD-L1+ tumors Incidence of trAEs: 60.6% for previously treated; 63.1% for PD-L1+ tumors | [25,26] |
KEYNOTE-335 (NCT02819518) | III | Previously untreated, locally recurrent, inoperable or metastatic TNBC |
| Median PFS: 9.7 months for arm (1); 5.6 months for arm (2) ORR: 53% for arm (1); 40% for arm (2) Incidence of trAEs: 68.1% for arm (1); 66.9% for arm (2) | [27] |
IMpower110 (NCT02409342) | III | Stage IV non-squamous or squamous non-small cell lung cancer |
| Median OS: 17.5 months for arm (1); 14.1 months for arm (2) Incidence of trAEs: 60.5% (grade 3 +: 12.9%) for arm (1); 85.2% (grade 3 +: 44.1%) for arm (2) | [31] |
IMpassion131 (NCT03125902) | III | Previously untreated, locally advanced or metastatic TNBC |
| Median PFS: 6.0 months for arm (1); 5.7 months for arm (2) Median OS: 22.8 months for arm (1); 22.1 months for arm (2) | [32] |
KEYNOTE-119 (NCT02555657) | III | Metastatic TNBC |
| Median PFS: 2.1 months for arm (1); 3.3 months for arm (2) Median OS: 9.9 months for arm (1); 10.8 months for arm (2) Incidence of grade 3+ trAEs: 14% for arm (1); 36% for arm (2) | [34] |
Trial (National Clinical Trial Identifier) | Phase | Condition | Interventions | Key Results | Reference |
---|---|---|---|---|---|
IMbrave150 (NCT03434379) | III | Locally advanced or metastatic solid tumors |
| Median PFS: 6.8 months for arm (1); 4.3 months for arm (2) Median OS: 2 months: 67.2% for arm (1); 54.6% for arm (2) Incidence of grade 3+ trAEs: 56.5% for arm (1); 55.1% for arm (2) | [81] |
(NCT02536469) | I | Advanced malignant solid tumors |
| No objective tumor responses observed, 73% had stable disease at week 24 Serum IL-8 significantly reduced on day 3, relative to baseline (p = 0.0004) Incidence of trAEs: 33% (mostly grade 1) | [85] |
MAGIC-8 (NCT03689699) | I/II | Hormone-sensitive prostate cancer |
| No preliminary data available, results expected in 2022 | [86] |
(NCT02754141) | I/II | Malignant solid tumors |
| Incidence of trAEs: N/A for arm (1); 58% for arm (2) Incidence of grade 3 trAEs: N/A for arm (1); 15% for arm (2) Overall, both arms (1) and (2) are well-tolerated | [87] |
(NCT01302405) | I | Advanced solid tumors |
| Incidence of trAEs: 17% Incidence of grade 3+ trAEs: 11.1%PRI-724 has an acceptable toxicity profile | [88] |
SYNERGY (NCT03616886) | I/II | Previously untreated, locally recurrent, inoperable or metastatic TNBC |
| No preliminary data available, results expected in 2023 | [89] |
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Mediratta, K.; El-Sahli, S.; D’Costa, V.; Wang, L. Current Progresses and Challenges of Immunotherapy in Triple-Negative Breast Cancer. Cancers 2020, 12, 3529. https://doi.org/10.3390/cancers12123529
Mediratta K, El-Sahli S, D’Costa V, Wang L. Current Progresses and Challenges of Immunotherapy in Triple-Negative Breast Cancer. Cancers. 2020; 12(12):3529. https://doi.org/10.3390/cancers12123529
Chicago/Turabian StyleMediratta, Karan, Sara El-Sahli, Vanessa D’Costa, and Lisheng Wang. 2020. "Current Progresses and Challenges of Immunotherapy in Triple-Negative Breast Cancer" Cancers 12, no. 12: 3529. https://doi.org/10.3390/cancers12123529