Targeting the Tumor Microenvironment for Improving Therapeutic Effectiveness in Cancer Immunotherapy: Focusing on Immune Checkpoint Inhibitors and Combination Therapies
Abstract
:Simple Summary
Abstract
1. Introduction
2. Tumor Microenvironment and Cancer Immunotherapy with ICIs
3. ICI Combination Therapy
4. Cancer Immunotherapy and Anti-Angiogenic Drugs
5. Combination of ICIs and Radiotherapy
6. Combination of Cancer Vaccines and ICIs
7. Genetically Modified T-Cell-Based Adoptive Immunotherapy
8. Immune Metabolism in Cancer Immunotherapy
9. Cancer Immunotherapy and the Gut Microbiota
10. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
- Davids, M.S.; Kim, H.T.; Bachireddy, P.; Costello, C.; Liguori, R.; Savell, A.; Lukez, A.P.; Avigan, D.; Chen, Y.B.; McSweeney, P.; et al. Ipilimumab for Patients with Relapse after Allogeneic Transplantation. N. Engl. J. Med. 2016, 375, 143–153. [Google Scholar] [CrossRef] [PubMed]
- Hodi, F.S.; O’Day, S.J.; McDermott, D.F.; Weber, R.W.; Sosman, J.A.; Haanen, J.B.; Gonzalez, R.; Robert, C.; Schadendorf, D.; Hassel, J.C.; et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 2010, 363, 711–723. [Google Scholar] [CrossRef] [PubMed]
- 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 Untreated Melanoma. N. Engl. J. Med. 2015, 373, 23–34. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Postow, M.A.; Chesney, J.; Pavlick, A.C.; Robert, C.; Grossmann, K.; McDermott, D.; Linette, G.P.; Meyer, N.; Giguere, J.K.; Agarwala, S.S.; et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N. Engl. J. Med. 2015, 372, 2006–2017. [Google Scholar] [CrossRef] [Green Version]
- Robert, C.; Ribas, A.; Wolchok, J.D.; Hodi, F.S.; Hamid, O.; Kefford, R.; Weber, J.S.; Joshua, A.M.; Hwu, W.J.; Gangadhar, T.C.; et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: A randomised dose-comparison cohort of a phase 1 trial. Lancet 2014, 384, 1109–1117. [Google Scholar] [CrossRef]
- Topalian, S.L.; Hodi, F.S.; Brahmer, J.R.; Gettinger, S.N.; Smith, D.C.; McDermott, D.F.; Powderly, J.D.; Carvajal, R.D.; Sosman, J.A.; Atkins, M.B.; et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 2012, 366, 2443–2454. [Google Scholar] [CrossRef]
- Weber, J.S.; Gibney, G.; Sullivan, R.J.; Sosman, J.A.; Slingluff, C.L., Jr.; Lawrence, D.P.; Logan, T.F.; Schuchter, L.M.; Nair, S.; Fecher, L.; et al. Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): An open-label, randomised, phase 2 trial. Lancet Oncol. 2016, 17, 943–955. [Google Scholar] [CrossRef] [Green Version]
- Francis, D.M.; Manspeaker, M.P.; Schudel, A.; Sestito, L.F.; O’Melia, M.J.; Kissick, H.T.; Pollack, B.P.; Waller, E.K.; Thomas, S.N. Blockade of immune checkpoints in lymph nodes through locoregional delivery augments cancer immunotherapy. Sci. Transl. Med. 2020, 12. [Google Scholar] [CrossRef]
- Leach, D.R.; Krummel, M.F.; Allison, J.P. Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996, 271, 1734–1736. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Freeman, G.J.; Long, A.J.; Iwai, Y.; Bourque, K.; Chernova, T.; Nishimura, H.; Fitz, L.J.; Malenkovich, N.; Okazaki, T.; Byrne, M.C.; et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 2000, 192, 1027–1034. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ribas, A.; Wolchok, J.D. Cancer immunotherapy using checkpoint blockade. Science 2018, 359, 1350–1355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fesnak, A.D.; June, C.H.; Levine, B.L. Engineered T cells: The promise and challenges of cancer immunotherapy. Nat. Rev. Cancer 2016, 16, 566–581. [Google Scholar] [CrossRef]
- June, C.H.; O’Connor, R.S.; Kawalekar, O.U.; Ghassemi, S.; Milone, M.C. CAR T cell immunotherapy for human cancer. Science 2018, 359, 1361–1365. [Google Scholar] [CrossRef] [Green Version]
- Maleki Vareki, S.; Garrigos, C.; Duran, I. Biomarkers of response to PD-1/PD-L1 inhibition. Crit. Rev. Oncol. Hematol. 2017, 116, 116–124. [Google Scholar] [CrossRef]
- Duluc, D.; Corvaisier, M.; Blanchard, S.; Catala, L.; Descamps, P.; Gamelin, E.; Ponsoda, S.; Delneste, Y.; Hebbar, M.; Jeannin, P. Interferon-gamma reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor-associated macrophages. Int. J. Cancer 2009, 125, 367–373. [Google Scholar] [CrossRef]
- Qian, B.Z.; Pollard, J.W. Macrophage diversity enhances tumor progression and metastasis. Cell 2010, 141, 39–51. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gabrilovich, D.I.; Ostrand-Rosenberg, S.; Bronte, V. Coordinated regulation of myeloid cells by tumours. Nat. Rev. Immunol. 2012, 12, 253–268. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rodig, N.; Ryan, T.; Allen, J.A.; Pang, H.; Grabie, N.; Chernova, T.; Greenfield, E.A.; Liang, S.C.; Sharpe, A.H.; Lichtman, A.H.; et al. Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis. Eur. J. Immunol. 2003, 33, 3117–3126. [Google Scholar] [CrossRef]
- Spranger, S.; Spaapen, R.M.; Zha, Y.; Williams, J.; Meng, Y.; Ha, T.T.; Gajewski, T.F. Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci. Transl. Med. 2013, 5, 200ra116. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Taube, J.M.; Anders, R.A.; Young, G.D.; Xu, H.; Sharma, R.; McMiller, T.L.; Chen, S.; Klein, A.P.; Pardoll, D.M.; Topalian, S.L.; et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci. Transl. Med. 2012, 4, 127ra137. [Google Scholar] [CrossRef] [Green Version]
- Pelster, M.S.; Amaria, R.N. Combined targeted therapy and immunotherapy in melanoma: A review of the impact on the tumor microenvironment and outcomes of early clinical trials. Ther. Adv. Med. Oncol. 2019, 11, 1758835919830826. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zappasodi, R.; Merghoub, T.; Wolchok, J.D. Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies. Cancer Cell 2018, 33, 581–598. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Syn, N.L.; Teng, M.W.L.; Mok, T.S.K.; Soo, R.A. De-novo and acquired resistance to immune checkpoint targeting. Lancet Oncol. 2017, 18, e731–e741. [Google Scholar] [CrossRef]
- Newman, A.M.; Liu, C.L.; Green, M.R.; Gentles, A.J.; Feng, W.; Xu, Y.; Hoang, C.D.; Diehn, M.; Alizadeh, A.A. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 2015, 12, 453–457. [Google Scholar] [CrossRef] [Green Version]
- Aran, D.; Hu, Z.; Butte, A.J. xCell: Digitally portraying the tissue cellular heterogeneity landscape. Genome Biol. 2017, 18, 220. [Google Scholar] [CrossRef] [Green Version]
- Bindea, G.; Mlecnik, B.; Tosolini, M.; Kirilovsky, A.; Waldner, M.; Obenauf, A.C.; Angell, H.; Fredriksen, T.; Lafontaine, L.; Berger, A.; et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 2013, 39, 782–795. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cruz, E.; Kayser, V. Monoclonal antibody therapy of solid tumors: Clinical limitations and novel strategies to enhance treatment efficacy. Biologics 2019, 13, 33–51. [Google Scholar] [CrossRef] [Green Version]
- Twyman-Saint Victor, C.; Rech, A.J.; Maity, A.; Rengan, R.; Pauken, K.E.; Stelekati, E.; Benci, J.L.; Xu, B.; Dada, H.; Odorizzi, P.M.; et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 2015, 520, 373–377. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Snyder, A.; Makarov, V.; Merghoub, T.; Yuan, J.; Zaretsky, J.M.; Desrichard, A.; Walsh, L.A.; Postow, M.A.; Wong, P.; Ho, T.S.; et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N. Engl. J. Med. 2014, 371, 2189–2199. [Google Scholar] [CrossRef] [PubMed]
- Rizvi, N.A.; Hellmann, M.D.; Snyder, A.; Kvistborg, P.; Makarov, V.; Havel, J.J.; Lee, W.; Yuan, J.; Wong, P.; Ho, T.S.; et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015, 348, 124–128. [Google Scholar] [CrossRef] [Green Version]
- Horn, L.; Mansfield, A.S.; Szczesna, A.; Havel, L.; Krzakowski, M.; Hochmair, M.J.; Huemer, F.; Losonczy, G.; Johnson, M.L.; Nishio, M.; et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 379, 2220–2229. [Google Scholar] [CrossRef]
- Motzer, R.J.; Tannir, N.M.; McDermott, D.F.; Aren Frontera, O.; Melichar, B.; Choueiri, T.K.; Plimack, E.R.; Barthelemy, P.; Porta, C.; George, S.; et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N. Engl. J. Med. 2018, 378, 1277–1290. [Google Scholar] [CrossRef] [PubMed]
- Galon, J.; Bruni, D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat. Rev. Drug Discov. 2019, 18, 197–218. [Google Scholar] [CrossRef] [PubMed]
- Huang, R.Y.; Francois, A.; McGray, A.R.; Miliotto, A.; Odunsi, K. Compensatory upregulation of PD-1, LAG-3, and CTLA-4 limits the efficacy of single-agent checkpoint blockade in metastatic ovarian cancer. Oncoimmunology 2017, 6, e1249561. [Google Scholar] [CrossRef] [Green Version]
- Fares, C.M.; Van Allen, E.M.; Drake, C.G.; Allison, J.P.; Hu-Lieskovan, S. Mechanisms of Resistance to Immune Checkpoint Blockade: Why Does Checkpoint Inhibitor Immunotherapy Not Work for All Patients? Am. Soc. Clin. Oncol. Educ. Book 2019, 39, 147–164. [Google Scholar] [CrossRef] [PubMed]
- Anderson, A.C.; Joller, N.; Kuchroo, V.K. Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation. Immunity 2016, 44, 989–1004. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhu, C.; Anderson, A.C.; Schubart, A.; Xiong, H.; Imitola, J.; Khoury, S.J.; Zheng, X.X.; Strom, T.B.; Kuchroo, V.K. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat. Immunol. 2005, 6, 1245–1252. [Google Scholar] [CrossRef] [PubMed]
- Dankner, M.; Gray-Owen, S.D.; Huang, Y.H.; Blumberg, R.S.; Beauchemin, N. CEACAM1 as a multi-purpose target for cancer immunotherapy. Oncoimmunology 2017, 6, e1328336. [Google Scholar] [CrossRef] [Green Version]
- Golden-Mason, L.; Palmer, B.E.; Kassam, N.; Townshend-Bulson, L.; Livingston, S.; McMahon, B.J.; Castelblanco, N.; Kuchroo, V.; Gretch, D.R.; Rosen, H.R. Negative immune regulator Tim-3 is overexpressed on T cells in hepatitis C virus infection and its blockade rescues dysfunctional CD4+ and CD8+ T cells. J. Virol. 2009, 83, 9122–9130. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yan, J.; Zhang, Y.; Zhang, J.P.; Liang, J.; Li, L.; Zheng, L. Tim-3 expression defines regulatory T cells in human tumors. PLoS ONE 2013, 8, e58006. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bialkowski, L.; Van der Jeught, K.; Bevers, S.; Tjok Joe, P.; Renmans, D.; Heirman, C.; Aerts, J.L.; Thielemans, K. Immune checkpoint blockade combined with IL-6 and TGF-beta inhibition improves the therapeutic outcome of mRNA-based immunotherapy. Int. J. Cancer 2018, 143, 686–698. [Google Scholar] [CrossRef]
- Popovic, A.; Jaffee, E.M.; Zaidi, N. Emerging strategies for combination checkpoint modulators in cancer immunotherapy. J. Clin. Investig. 2018, 128, 3209–3218. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dougall, W.C.; Kurtulus, S.; Smyth, M.J.; Anderson, A.C. TIGIT and CD96: New checkpoint receptor targets for cancer immunotherapy. Immunol. Rev. 2017, 276, 112–120. [Google Scholar] [CrossRef] [PubMed]
- Chauvin, J.M.; Pagliano, O.; Fourcade, J.; Sun, Z.; Wang, H.; Sander, C.; Kirkwood, J.M.; Chen, T.H.; Maurer, M.; Korman, A.J.; et al. TIGIT and PD-1 impair tumor antigen-specific CD8(+) T cells in melanoma patients. J. Clin. Investig. 2015, 125, 2046–2058. [Google Scholar] [CrossRef] [PubMed]
- Terme, M.; Pernot, S.; Marcheteau, E.; Sandoval, F.; Benhamouda, N.; Colussi, O.; Dubreuil, O.; Carpentier, A.F.; Tartour, E.; Taieb, J. VEGFA-VEGFR pathway blockade inhibits tumor-induced regulatory T-cell proliferation in colorectal cancer. Cancer Res. 2013, 73, 539–549. [Google Scholar] [CrossRef] [Green Version]
- Li, S.; Liu, M.; Do, M.H.; Chou, C.; Stamatiades, E.G.; Nixon, B.G.; Shi, W.; Zhang, X.; Li, P.; Gao, S.; et al. Cancer immunotherapy via targeted TGF-beta signalling blockade in TH cells. Nature 2020, 587, 121–125. [Google Scholar] [CrossRef] [PubMed]
- Rini, B.I.; Powles, T.; Atkins, M.B.; Escudier, B.; McDermott, D.F.; Suarez, C.; Bracarda, S.; Stadler, W.M.; Donskov, F.; Lee, J.L.; et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): A multicentre, open-label, phase 3, randomised controlled trial. Lancet 2019, 393, 2404–2415. [Google Scholar] [CrossRef]
- Motzer, R.J.; Penkov, K.; Haanen, J.; Rini, B.; Albiges, L.; Campbell, M.T.; Venugopal, B.; Kollmannsberger, C.; Negrier, S.; Uemura, M.; et al. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N. Engl. J. Med. 2019, 380, 1103–1115. [Google Scholar] [CrossRef] [PubMed]
- Reck, M.; Mok, T.S.K.; Nishio, M.; Jotte, R.M.; Cappuzzo, F.; Orlandi, F.; Stroyakovskiy, D.; Nogami, N.; Rodriguez-Abreu, D.; Moro-Sibilot, D.; et al. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): Key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir. Med. 2019, 7, 387–401. [Google Scholar] [CrossRef]
- 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]
- Wen, P.; Gao, Y.; Chen, B.; Qi, X.; Hu, G.; Xu, A.; Xia, J.; Wu, L.; Lu, H.; Zhao, G. Pan-Cancer Analysis of Radiotherapy Benefits and Immune Infiltration in Multiple Human Cancers. Cancers 2020, 12, 957. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Demaria, S.; Kawashima, N.; Yang, A.M.; Devitt, M.L.; Babb, J.S.; Allison, J.P.; Formenti, S.C. Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin. Cancer Res. 2005, 11 Pt 1, 728–734. [Google Scholar]
- Trommer, M.; Yeo, S.Y.; Persigehl, T.; Bunck, A.; Grull, H.; Schlaak, M.; Theurich, S.; von Bergwelt-Baildon, M.; Morgenthaler, J.; Herter, J.M.; et al. Abscopal Effects in Radio-Immunotherapy-Response Analysis of Metastatic Cancer Patients With Progressive Disease Under Anti-PD-1 Immune Checkpoint Inhibition. Front. Pharm. 2019, 10, 511. [Google Scholar] [CrossRef] [Green Version]
- De Forceville, L.; Deau-Fischer, B.; Franchi, P.; Arsene-Henry, A.; Cassou Mounat, T.; Bouscary, D.; Kirova, Y.M. Radiotherapy in combination with nivolumab for relapsed/refractory classical Hodgkin lymphoma: About two cases. Cancer Radiother. 2019, 23, 232–239. [Google Scholar] [CrossRef]
- Antonia, S.J.; Villegas, A.; Daniel, D.; Vicente, D.; Murakami, S.; Hui, R.; Yokoi, T.; Chiappori, A.; Lee, K.H.; de Wit, M.; et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2017, 377, 1919–1929. [Google Scholar] [CrossRef] [PubMed]
- Gong, J.; Le, T.Q.; Massarelli, E.; Hendifar, A.E.; Tuli, R. Radiation therapy and PD-1/PD-L1 blockade: The clinical development of an evolving anticancer combination. J. Immunother. Cancer 2018, 6, 46. [Google Scholar] [CrossRef] [PubMed]
- Pardi, N.; Hogan, M.J.; Porter, F.W.; Weissman, D. mRNA vaccines—A new era in vaccinology. Nat. Rev. Drug Discov. 2018, 17, 261–279. [Google Scholar] [CrossRef] [Green Version]
- Sahin, U.; Derhovanessian, E.; Miller, M.; Kloke, B.P.; Simon, P.; Lower, M.; Bukur, V.; Tadmor, A.D.; Luxemburger, U.; Schrors, B.; et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 2017, 547, 222–226. [Google Scholar] [CrossRef] [PubMed]
- Kos, S.; Lopes, A.; Preat, V.; Cemazar, M.; Lampreht Tratar, U.; Ucakar, B.; Vanvarenberg, K.; Sersa, G.; Vandermeulen, G. Intradermal DNA vaccination combined with dual CTLA-4 and PD-1 blockade provides robust tumor immunity in murine melanoma. PLoS ONE 2019, 14, e0217762. [Google Scholar] [CrossRef] [Green Version]
- Hailemichael, Y.; Woods, A.; Fu, T.; He, Q.; Nielsen, M.C.; Hasan, F.; Roszik, J.; Xiao, Z.; Vianden, C.; Khong, H.; et al. Cancer vaccine formulation dictates synergy with CTLA-4 and PD-L1 checkpoint blockade therapy. J. Clin. Investig. 2018, 128, 1338–1354. [Google Scholar] [CrossRef] [PubMed]
- D’Aloia, M.M.; Zizzari, I.G.; Sacchetti, B.; Pierelli, L.; Alimandi, M. CAR-T cells: The long and winding road to solid tumors. Cell Death Dis. 2018, 9, 282. [Google Scholar] [CrossRef] [PubMed]
- Brudno, J.N.; Kochenderfer, J.N. Toxicities of chimeric antigen receptor T cells: Recognition and management. Blood 2016, 127, 3321–3330. [Google Scholar] [CrossRef] [Green Version]
- Cao, Y.; Lu, W.; Sun, R.; Jin, X.; Cheng, L.; He, X.; Wang, L.; Yuan, T.; Lyu, C.; Zhao, M. Anti-CD19 Chimeric Antigen Receptor T Cells in Combination With Nivolumab Are Safe and Effective Against Relapsed/Refractory B-Cell Non-hodgkin Lymphoma. Front. Oncol. 2019, 9, 767. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, J.; Deng, Q.; Jiang, Y.Y.; Zhang, R.; Zhu, H.B.; Meng, J.X.; Li, Y.M. CAR-T 19 combined with reduced-dose PD-1 blockade therapy for treatment of refractory follicular lymphoma: A case report. Oncol. Lett. 2019, 18, 4415–4420. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, S.; Siriwon, N.; Zhang, X.; Yang, S.; Jin, T.; He, F.; Kim, Y.J.; Mac, J.; Lu, Z.; Wang, S.; et al. Enhanced Cancer Immunotherapy by Chimeric Antigen Receptor-Modified T Cells Engineered to Secrete Checkpoint Inhibitors. Clin. Cancer Res. 2017, 23, 6982–6992. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rafiq, S.; Yeku, O.O.; Jackson, H.J.; Purdon, T.J.; van Leeuwen, D.G.; Drakes, D.J.; Song, M.; Miele, M.M.; Li, Z.; Wang, P.; et al. Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo. Nat. Biotechnol. 2018, 36, 847–856. [Google Scholar] [CrossRef] [PubMed]
- Nakazawa, T.; Natsume, A.; Nishimura, F.; Morimoto, T.; Matsuda, R.; Nakamura, M.; Yamada, S.; Nakagawa, I.; Motoyama, Y.; Park, Y.S.; et al. Effect of CRISPR/Cas9-Mediated PD-1-Disrupted Primary Human Third-Generation CAR-T Cells Targeting EGFRvIII on In Vitro Human Glioblastoma Cell Growth. Cells 2020, 9, 998. [Google Scholar] [CrossRef] [PubMed]
- Viale, A.; Draetta, G.F. Metabolic Features of Cancer Treatment Resistance. Recent Results Cancer Res. 2016, 207, 135–156. [Google Scholar] [CrossRef] [PubMed]
- Sica, A.; Larghi, P.; Mancino, A.; Rubino, L.; Porta, C.; Totaro, M.G.; Rimoldi, M.; Biswas, S.K.; Allavena, P.; Mantovani, A. Macrophage polarization in tumour progression. Semin. Cancer Biol. 2008, 18, 349–355. [Google Scholar] [CrossRef] [PubMed]
- Veglia, F.; Perego, M.; Gabrilovich, D. Myeloid-derived suppressor cells coming of age. Nat. Immunol. 2018, 19, 108–119. [Google Scholar] [CrossRef] [PubMed]
- MacIver, N.J.; Michalek, R.D.; Rathmell, J.C. Metabolic regulation of T lymphocytes. Annu. Rev. Immunol. 2013, 31, 259–283. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- 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-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J. Exp. Med. 2014, 211, 781–790. [Google Scholar] [CrossRef] [PubMed]
- Murphy, K.A.; James, B.R.; Sjaastad, F.V.; Kucaba, T.A.; Kim, H.; Brincks, E.L.; Chua, S.C., Jr.; Wilber, A.; Griffith, T.S. Cutting Edge: Elevated Leptin during Diet-Induced Obesity Reduces the Efficacy of Tumor Immunotherapy. J. Immunol. 2018, 201, 1837–1841. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cortellini, A.; Bersanelli, M.; Buti, S.; Cannita, K.; Santini, D.; Perrone, F.; Giusti, R.; Tiseo, M.; Michiara, M.; Di Marino, P.; et al. A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: When overweight becomes favorable. J. Immunother. Cancer 2019, 7, 57. [Google Scholar] [CrossRef]
- Chamoto, K.; Chowdhury, P.S.; Kumar, A.; Sonomura, K.; Matsuda, F.; Fagarasan, S.; Honjo, T. Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity. Proc. Natl. Acad. Sci. USA 2017, 114, E761–E770. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.; Kurupati, R.; Liu, L.; Zhou, X.Y.; Zhang, G.; Hudaihed, A.; Filisio, F.; Giles-Davis, W.; Xu, X.; Karakousis, G.C.; et al. Enhancing CD8(+) T Cell Fatty Acid Catabolism within a Metabolically Challenging Tumor Microenvironment Increases the Efficacy of Melanoma Immunotherapy. Cancer Cell 2017, 32, 377–391. [Google Scholar] [CrossRef] [Green Version]
- Sivan, A.; Corrales, L.; Hubert, N.; Williams, J.B.; Aquino-Michaels, K.; Earley, Z.M.; Benyamin, F.W.; Lei, Y.M.; Jabri, B.; Alegre, M.L.; et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 2015, 350, 1084–1089. [Google Scholar] [CrossRef] [Green Version]
- Routy, B.; Le Chatelier, E.; Derosa, L.; Duong, C.P.M.; Alou, M.T.; Daillere, R.; Fluckiger, A.; Messaoudene, M.; Rauber, C.; Roberti, M.P.; et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 2018, 359, 91–97. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gopalakrishnan, V.; Spencer, C.N.; Nezi, L.; Reuben, A.; Andrews, M.C.; Karpinets, T.V.; Prieto, P.A.; Vicente, D.; Hoffman, K.; Wei, S.C.; et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 2018, 359, 97–103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vetizou, M.; Pitt, J.M.; Daillere, R.; Lepage, P.; Waldschmitt, N.; Flament, C.; Rusakiewicz, S.; Routy, B.; Roberti, M.P.; Duong, C.P.; et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 2015, 350, 1079–1084. [Google Scholar] [CrossRef] [Green Version]
- Gur, C.; Ibrahim, Y.; Isaacson, B.; Yamin, R.; Abed, J.; Gamliel, M.; Enk, J.; Bar-On, Y.; Stanietsky-Kaynan, N.; Coppenhagen-Glazer, S.; et al. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 2015, 42, 344–355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Chyuan, I.-T.; Chu, C.-L.; Hsu, P.-N. Targeting the Tumor Microenvironment for Improving Therapeutic Effectiveness in Cancer Immunotherapy: Focusing on Immune Checkpoint Inhibitors and Combination Therapies. Cancers 2021, 13, 1188. https://doi.org/10.3390/cancers13061188
Chyuan I-T, Chu C-L, Hsu P-N. Targeting the Tumor Microenvironment for Improving Therapeutic Effectiveness in Cancer Immunotherapy: Focusing on Immune Checkpoint Inhibitors and Combination Therapies. Cancers. 2021; 13(6):1188. https://doi.org/10.3390/cancers13061188
Chicago/Turabian StyleChyuan, I-Tsu, Ching-Liang Chu, and Ping-Ning Hsu. 2021. "Targeting the Tumor Microenvironment for Improving Therapeutic Effectiveness in Cancer Immunotherapy: Focusing on Immune Checkpoint Inhibitors and Combination Therapies" Cancers 13, no. 6: 1188. https://doi.org/10.3390/cancers13061188
APA StyleChyuan, I.-T., Chu, C.-L., & Hsu, P.-N. (2021). Targeting the Tumor Microenvironment for Improving Therapeutic Effectiveness in Cancer Immunotherapy: Focusing on Immune Checkpoint Inhibitors and Combination Therapies. Cancers, 13(6), 1188. https://doi.org/10.3390/cancers13061188