Fibroblasts Influence the Efficacy, Resistance, and Future Use of Vaccines and Immunotherapy in Cancer Treatment
Abstract
:1. Introduction
1.1. Fibroblasts in Cancer
1.1.1. Normal versus Cancer-Associated Fibroblasts
1.1.2. Release of Cytokines and Chemokines
1.2. Cancer Immunotherapy and Vaccines
1.2.1. Cancer Immunotherapy
1.2.2. Cancer Vaccines
2. Effects of Fibroblasts on Response to Cancer Immunotherapy Treatment
2.1. Fibroblasts and Their Effects on Immune Cells and Immunotherapy Treatment
2.1.1. Fibroblasts and Innate Immune Cells
2.1.2. Fibroblasts and Adaptive Immune Cells
2.1.3. Fibroblasts and Efficacy of Immunotherapy
2.2. Predictors of Immunotherapy Response and Attempts at Their Therapeutic Targeting
2.2.1. Fibroblast Activation Protein
2.2.2. TGF-β
3. Targeting of CAFs with Immunotherapy
3.1. CAF-Targeting Vaccines
3.2. CAR T-Cells
4. Conclusions and Future Directions
Funding
Conflicts of Interest
References
- Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin. 2020, 70, 7–30. [Google Scholar] [CrossRef] [PubMed]
- Chu, G.C.; Kimmelman, A.C.; Hezel, A.F.; DePinho, R.A. Stromal biology of pancreatic cancer. J. Cell Biochem. 2007, 101, 887–907. [Google Scholar] [CrossRef]
- Erkan, M.; Hausmann, S.; Michalski, C.W.; Fingerle, A.A.; Dobritz, M.; Kleeff, J.; Friess, H. The role of stroma in pancreatic cancer: Diagnostic and therapeutic implications. Nat. Rev. Gastroenterol. Hepatol. 2012, 9, 454–467. [Google Scholar] [CrossRef]
- Nurmik, M.; Ullmann, P.; Rodriguez, F.; Haan, S.; Letellier, E. In search of definitions: Cancer-associated fibroblasts and their markers. Int. J. Cancer 2020, 146, 895–905. [Google Scholar] [CrossRef] [Green Version]
- Sharma, P.; Hu-Lieskovan, S.; Wargo, J.A.; Ribas, A. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell 2017, 168, 707–723. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- O’Donnell, J.S.; Teng, M.W.L.; Smyth, M.J. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat. Rev. Clin. Oncol. 2019, 16, 151–167. [Google Scholar] [CrossRef] [PubMed]
- Bhatt, D.; Daemen, T. Therapeutic Vaccines and Cancer Immunotherapy. Vaccines 2020, 8, 596. [Google Scholar] [CrossRef] [PubMed]
- Rous, P. An Experimental Comparison of Transplanted Tumor and a Transplanted Normal Tissue Capable of Growth. J. Exp. Med. 1910, 12, 344–366. [Google Scholar] [CrossRef] [PubMed]
- Wang, M.; Zhao, J.; Zhang, L.; Wei, F.; Lian, Y.; Wu, Y.; Gong, Z.; Zhang, S.; Zhou, J.; Cao, K.; et al. Role of tumor microenvironment in tumorigenesis. J. Cancer 2017, 8, 761–773. [Google Scholar] [CrossRef] [PubMed]
- Roma-Rodrigues, C.; Mendes, R.; Baptista, P.V.; Fernandes, A.R. Targeting Tumor Microenvironment for Cancer Therapy. Int. J. Mol. Sci. 2019, 20, 840. [Google Scholar] [CrossRef] [Green Version]
- Dvorak, H.F. Tumors: Wounds that do not heal. Similarities between tumor stroma generation and wound healing. N. Engl. J. Med. 1986, 315, 1650–1659. [Google Scholar] [CrossRef] [PubMed]
- Rybinski, B.; Franco-Barraza, J.; Cukierman, E. The wound healing, chronic fibrosis, and cancer progression triad. Physiol. Genomics 2014, 46, 223–244. [Google Scholar] [CrossRef] [PubMed]
- Sahai, E.; Astsaturov, I.; Cukierman, E.; DeNardo, D.G.; Egeblad, M.; Evans, R.M.; Fearon, D.; Greten, F.R.; Hingorani, S.R.; Hunter, T.; et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer. 2020, 20, 174–186. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Karagiannis, G.S.; Poutahidis, T.; Erdman, S.E.; Kirsch, R.; Riddell, R.H.; Diamandis, E.P. Cancer-associated fibroblasts drive the progression of metastasis through both paracrine and mechanical pressure on cancer tissue. Mol. Cancer Res. 2012, 10, 1403–1418. [Google Scholar] [CrossRef] [Green Version]
- Piersma, B.; Hayward, M.K.; Weaver, V.M. Fibrosis and cancer: A strained relationship. Biochim. Biophys. Acta Rev. Cancer 2020, 1873, 188356. [Google Scholar] [CrossRef]
- Barrett, R.L.; Pure, E. Cancer-associated fibroblasts and their influence on tumor immunity and immunotherapy. Elife 2020, 9, e57243. [Google Scholar] [CrossRef] [PubMed]
- Goetz, J.G.; Minguet, S.; Navarro-Lerida, I.; Lazcano, J.J.; Samaniego, R.; Calvo, E.; Tello, M.; Osteso-Ibanez, T.; Pellinen, T.; Echarri, A.; et al. Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell 2011, 146, 148–163. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Webber, J.; Steadman, R.; Mason, M.D.; Tabi, Z.; Clayton, A. Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Res. 2010, 70, 9621–9630. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ohlund, D.; Handly-Santana, A.; Biffi, G.; Elyada, E.; Almeida, A.S.; Ponz-Sarvise, M.; Corbo, V.; Oni, T.E.; Hearn, S.A.; Lee, E.J.; et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J. Exp. Med. 2017, 214, 579–596. [Google Scholar] [CrossRef]
- Elyada, E.; Bolisetty, M.; Laise, P.; Flynn, W.F.; Courtois, E.T.; Burkhart, R.A.; Teinor, J.A.; Belleau, P.; Biffi, G.; Lucito, M.S.; et al. Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts. Cancer Discov. 2019, 9, 1102–1123. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Biffi, G.; Oni, T.E.; Spielman, B.; Hao, Y.; Elyada, E.; Park, Y.; Preall, J.; Tuveson, D.A. IL1-Induced JAK/STAT Signaling Is Antagonized by TGFbeta to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma. Cancer Discov. 2019, 9, 282–301. [Google Scholar] [CrossRef] [Green Version]
- Monteran, L.; Erez, N. The Dark Side of Fibroblasts: Cancer-Associated Fibroblasts as Mediators of Immunosuppression in the Tumor Microenvironment. Front. Immunol. 2019, 10, 1835. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fearon, D.T. The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillance. Cancer Immunol. Res. 2014, 2, 187–193. [Google Scholar] [CrossRef] [Green Version]
- Sherman, M.H. Stellate Cells in Tissue Repair, Inflammation, and Cancer. Annu. Rev. Cell Dev. Biol. 2018, 34, 333–355. [Google Scholar] [CrossRef] [PubMed]
- Helms, E.; Onate, M.K.; Sherman, M.H. Fibroblast Heterogeneity in the Pancreatic Tumor Microenvironment. Cancer Discov. 2020, 10, 648–656. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lazennec, G.; Richmond, A. Chemokines and chemokine receptors: New insights into cancer-related inflammation. Trends Mol. Med. 2010, 16, 133–144. [Google Scholar] [CrossRef] [Green Version]
- Orimo, A.; Gupta, P.B.; Sgroi, D.C.; Arenzana-Seisdedos, F.; Delaunay, T.; Naeem, R.; Carey, V.J.; Richardson, A.L.; Weinberg, R.A. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 2005, 121, 335–348. [Google Scholar] [CrossRef]
- Garber, K. First results for agents targeting cancer-related inflammation. J. Natl. Cancer Inst. 2009, 101, 1110–1112. [Google Scholar] [CrossRef]
- Pease, J.E.; Horuk, R. Chemokine receptor antagonists: Part 1. Expert Opin. Ther. Pat. 2009, 19, 39–58. [Google Scholar] [CrossRef] [PubMed]
- Pease, J.E.; Horuk, R. Chemokine receptor antagonists: Part 2. Expert Opin. Ther. Pat. 2009, 19, 199–221. [Google Scholar] [CrossRef]
- Wells, T.N.; Power, C.A.; Shaw, J.P.; Proudfoot, A.E. Chemokine blockers—Therapeutics in the making? Trends Pharmacol. Sci. 2006, 27, 41–47. [Google Scholar] [CrossRef] [PubMed]
- Zigler, M.; Villares, G.J.; Lev, D.C.; Melnikova, V.O.; Bar-Eli, M. Tumor immunotherapy in melanoma: Strategies for overcoming mechanisms of resistance and escape. Am. J. Clin. Dermatol. 2008, 9, 307–311. [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]
- Sharma, B.; Nawandar, D.M.; Nannuru, K.C.; Varney, M.L.; Singh, R.K. Targeting CXCR2 enhances chemotherapeutic response, inhibits mammary tumor growth, angiogenesis, and lung metastasis. Mol. Cancer Ther. 2013, 12, 799–808. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Young, H.L.; Rowling, E.J.; Bugatti, M.; Giurisato, E.; Luheshi, N.; Arozarena, I.; Acosta, J.C.; Kamarashev, J.; Frederick, D.T.; Cooper, Z.A.; et al. An adaptive signaling network in melanoma inflammatory niches confers tolerance to MAPK signaling inhibition. J. Exp. Med. 2017, 214, 1691–1710. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Devapatla, B.; Sharma, A.; Woo, S. CXCR2 Inhibition Combined with Sorafenib Improved Antitumor and Antiangiogenic Response in Preclinical Models of Ovarian Cancer. PLoS ONE 2015, 10, e0139237. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nywening, T.M.; Belt, B.A.; Cullinan, D.R.; Panni, R.Z.; Han, B.J.; Sanford, D.E.; Jacobs, R.C.; Ye, J.; Patel, A.A.; Gillanders, W.E.; et al. Targeting both tumour-associated CXCR2(+) neutrophils and CCR2(+) macrophages disrupts myeloid recruitment and improves chemotherapeutic responses in pancreatic ductal adenocarcinoma. Gut 2018, 67, 1112–1123. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mollica Poeta, V.; Massara, M.; Capucetti, A.; Bonecchi, R. Chemokines and Chemokine Receptors: New Targets for Cancer Immunotherapy. Front. Immunol. 2019, 10, 379. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Couzin-Frankel, J. Breakthrough of the year 2013. Cancer Immunother. Sci. 2013, 342, 1432–1433. [Google Scholar] [CrossRef] [Green Version]
- Waldman, A.D.; Fritz, J.M.; Lenardo, M.J. A guide to cancer immunotherapy: From T cell basic science to clinical practice. Nat. Rev. Immunol. 2020, 20, 651–668. [Google Scholar] [CrossRef]
- Hodi, F.S.; Mihm, M.C.; Soiffer, R.J.; Haluska, F.G.; Butler, M.; Seiden, M.V.; Davis, T.; Henry-Spires, R.; MacRae, S.; Willman, A.; et al. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc. Natl. Acad. Sci. USA 2003, 100, 4712–4717. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Weber, J.S.; D’Angelo, S.P.; Minor, D.; Hodi, F.S.; Gutzmer, R.; Neyns, B.; Hoeller, C.; Khushalani, N.I.; Miller, W.H., Jr.; Lao, C.D.; et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): A randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015, 16, 375–384. [Google Scholar] [CrossRef]
- Weber, J.; Mandala, M.; Del Vecchio, M.; Gogas, H.J.; 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]
- Robert, C.; Long, G.V.; Brady, B.; Dutriaux, C.; Maio, M.; Mortier, L.; Hassel, J.C.; Rutkowski, P.; McNeil, C.; Kalinka-Warzocha, E.; et al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 2015, 372, 320–330. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Herbst, R.S.; Baas, P.; Kim, D.W.; Felip, E.; Perez-Gracia, J.L.; Han, J.Y.; Molina, J.; Kim, J.H.; Arvis, C.D.; Ahn, M.J.; et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet 2016, 387, 1540–1550. [Google Scholar] [CrossRef]
- Reck, M.; Rodriguez-Abreu, D.; Robinson, A.G.; Hui, R.; Csoszi, T.; Fulop, A.; Gottfried, M.; Peled, N.; Tafreshi, A.; Cuffe, S.; et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2016, 375, 1823–1833. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cohen, E.E.W.; Soulieres, D.; Le Tourneau, C.; Dinis, J.; Licitra, L.; Ahn, M.J.; Soria, A.; Machiels, J.P.; Mach, N.; Mehra, R.; et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): A randomised, open-label, phase 3 study. Lancet 2019, 393, 156–167. [Google Scholar] [CrossRef]
- Chen, R.; Zinzani, P.L.; Lee, H.J.; Armand, P.; Johnson, N.A.; Brice, P.; Radford, J.; Ribrag, V.; Molin, D.; Vassilakopoulos, T.P.; et al. Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087. Blood 2019, 134, 1144–1153. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bellmunt, J.; de Wit, R.; Vaughn, D.J.; Fradet, Y.; Lee, J.L.; Fong, L.; Vogelzang, N.J.; Climent, M.A.; Petrylak, D.P.; Choueiri, T.K.; et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N. Engl. J. Med. 2017, 376, 1015–1026. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Motzer, R.J.; Escudier, B.; McDermott, D.F.; George, S.; Hammers, H.J.; Srinivas, S.; Tykodi, S.S.; Sosman, J.A.; Procopio, G.; Plimack, E.R.; et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N. Engl. J. Med. 2015, 373, 1803–1813. [Google Scholar] [CrossRef] [PubMed]
- Ferris, R.L.; Blumenschein, G., Jr.; Fayette, J.; Guigay, J.; Colevas, A.D.; Licitra, L.; Harrington, K.; Kasper, S.; Vokes, E.E.; Even, C.; et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N. Engl. J. Med. 2016, 375, 1856–1867. [Google Scholar] [CrossRef]
- Sharma, P.; Retz, M.; Siefker-Radtke, A.; Baron, A.; Necchi, A.; Bedke, J.; Plimack, E.R.; Vaena, D.; Grimm, M.O.; Bracarda, S.; et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): A multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017, 18, 312–322. [Google Scholar] [CrossRef]
- Ansell, S.M.; Lesokhin, A.M.; Borrello, I.; Halwani, A.; Scott, E.C.; Gutierrez, M.; Schuster, S.J.; Millenson, M.M.; Cattry, D.; Freeman, G.J.; et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N. Engl. J. Med. 2015, 372, 311–319. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Overman, M.J.; McDermott, R.; Leach, J.L.; Lonardi, S.; Lenz, H.J.; Morse, M.A.; Desai, J.; Hill, A.; Axelson, M.; Moss, R.A.; et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): An open-label, multicentre, phase 2 study. Lancet Oncol. 2017, 18, 1182–1191. [Google Scholar] [CrossRef]
- Rosenberg, S.A.; Packard, B.S.; Aebersold, P.M.; Solomon, D.; Topalian, S.L.; Toy, S.T.; Simon, P.; Lotze, M.T.; Yang, J.C.; Seipp, C.A.; et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N. Engl. J. Med. 1988, 319, 1676–1680. [Google Scholar] [CrossRef] [PubMed]
- Rosenberg, S.A.; Yannelli, J.R.; Yang, J.C.; Topalian, S.L.; Schwartzentruber, D.J.; Weber, J.S.; Parkinson, D.R.; Seipp, C.A.; Einhorn, J.H.; White, D.E. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J. Natl. Cancer Inst. 1994, 86, 1159–1166. [Google Scholar] [CrossRef]
- Rosenberg, S.A.; Yang, J.C.; Sherry, R.M.; Kammula, U.S.; Hughes, M.S.; Phan, G.Q.; Citrin, D.E.; Restifo, N.P.; Robbins, P.F.; Wunderlich, J.R.; et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin. Cancer Res. 2011, 17, 4550–4557. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Park, J.H.; Riviere, I.; Gonen, M.; Wang, X.; Senechal, B.; Curran, K.J.; Sauter, C.; Wang, Y.; Santomasso, B.; Mead, E.; et al. Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. N. Engl. J. Med. 2018, 378, 449–459. [Google Scholar] [CrossRef] [PubMed]
- Neelapu, S.S.; Locke, F.L.; Bartlett, N.L.; Lekakis, L.J.; Miklos, D.B.; Jacobson, C.A.; Braunschweig, I.; Oluwole, O.O.; Siddiqi, T.; Lin, Y.; et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N. Engl. J. Med. 2017, 377, 2531–2544. [Google Scholar] [CrossRef] [PubMed]
- Beatty, G.L.; Haas, A.R.; Maus, M.V.; Torigian, D.A.; Soulen, M.C.; Plesa, G.; Chew, A.; Zhao, Y.; Levine, B.L.; Albelda, S.M.; et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol. Res. 2014, 2, 112–120. [Google Scholar] [CrossRef] [Green Version]
- Kershaw, M.H.; Westwood, J.A.; Parker, L.L.; Wang, G.; Eshhar, Z.; Mavroukakis, S.A.; White, D.E.; Wunderlich, J.R.; Canevari, S.; Rogers-Freezer, L.; et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin. Cancer Res. 2006, 12, 6106–6115. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Park, J.R.; Digiusto, D.L.; Slovak, M.; Wright, C.; Naranjo, A.; Wagner, J.; Meechoovet, H.B.; Bautista, C.; Chang, W.C.; Ostberg, J.R.; et al. Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Mol. Ther. 2007, 15, 825–833. [Google Scholar] [CrossRef] [PubMed]
- Lawler, S.E.; Speranza, M.C.; Cho, C.F.; Chiocca, E.A. Oncolytic Viruses in Cancer Treatment: A Review. JAMA Oncol. 2017, 3, 841–849. [Google Scholar] [CrossRef] [Green Version]
- Stojdl, D.F.; Lichty, B.; Knowles, S.; Marius, R.; Atkins, H.; Sonenberg, N.; Bell, J.C. Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat. Med. 2000, 6, 821–825. [Google Scholar] [CrossRef] [PubMed]
- Aghi, M.; Visted, T.; Depinho, R.A.; Chiocca, E.A. Oncolytic herpes virus with defective ICP6 specifically replicates in quiescent cells with homozygous genetic mutations in p16. Oncogene 2008, 27, 4249–4254. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Coffey, M.C.; Strong, J.E.; Forsyth, P.A.; Lee, P.W. Reovirus therapy of tumors with activated Ras pathway. Science 1998, 282, 1332–1334. [Google Scholar] [CrossRef]
- Pol, J.; Kroemer, G.; Galluzzi, L. First oncolytic virus approved for melanoma immunotherapy. Oncoimmunology 2016, 5, e1115641. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, B.L.; Robinson, M.; Han, Z.Q.; Branston, R.H.; English, C.; Reay, P.; McGrath, Y.; Thomas, S.K.; Thornton, M.; Bullock, P.; et al. ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther. 2003, 10, 292–303. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kaufman, H.L.; Bines, S.D. OPTIM trial: A Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma. Future Oncol. 2010, 6, 941–949. [Google Scholar] [CrossRef] [PubMed]
- Andtbacka, R.H.; Kaufman, H.L.; Collichio, F.; Amatruda, T.; Senzer, N.; Chesney, J.; Delman, K.A.; Spitler, L.E.; Puzanov, I.; Agarwala, S.S.; et al. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J. Clin. Oncol. 2015, 33, 2780–2788. [Google Scholar] [CrossRef]
- Guo, C.; Manjili, M.H.; Subjeck, J.R.; Sarkar, D.; Fisher, P.B.; Wang, X.Y. Therapeutic cancer vaccines: Past, present, and future. Adv. Cancer Res. 2013, 119, 421–475. [Google Scholar] [CrossRef] [Green Version]
- Morales, A.; Eidinger, D.; Bruce, A.W. Intracavitary Bacillus Calmette-Guerin in the Treatment of Superficial Bladder Tumors. J. Urol. 2017, 197, S142–S145. [Google Scholar] [CrossRef]
- Hanna, M.G., Jr.; Peters, L.C. Immunotherapy of established micrometastases with Bacillus Calmette-Guerin tumor cell vaccine. Cancer Res. 1978, 38, 204–209. [Google Scholar]
- Constantino, J.; Gomes, C.; Falcao, A.; Cruz, M.T.; Neves, B.M. Antitumor dendritic cell-based vaccines: Lessons from 20 years of clinical trials and future perspectives. Transl. Res. 2016, 168, 74–95. [Google Scholar] [CrossRef] [PubMed]
- Kantoff, P.W.; Higano, C.S.; Shore, N.D.; Berger, E.R.; Small, E.J.; Penson, D.F.; Redfern, C.H.; Ferrari, A.C.; Dreicer, R.; Sims, R.B.; et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 2010, 363, 411–422. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tel, J.; Aarntzen, E.H.; Baba, T.; Schreibelt, G.; Schulte, B.M.; Benitez-Ribas, D.; Boerman, O.C.; Croockewit, S.; Oyen, W.J.; van Rossum, M.; et al. Natural human plasmacytoid dendritic cells induce antigen-specific T-cell responses in melanoma patients. Cancer Res. 2013, 73, 1063–1075. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Van Tendeloo, V.F.; Van de Velde, A.; Van Driessche, A.; Cools, N.; Anguille, S.; Ladell, K.; Gostick, E.; Vermeulen, K.; Pieters, K.; Nijs, G.; et al. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms’ tumor 1 antigen-targeted dendritic cell vaccination. Proc. Natl. Acad. Sci. USA 2010, 107, 13824–13829. [Google Scholar] [CrossRef] [Green Version]
- Rosenblatt, J.; Avivi, I.; Vasir, B.; Uhl, L.; Munshi, N.C.; Katz, T.; Dey, B.R.; Somaiya, P.; Mills, H.; Campigotto, F.; et al. Vaccination with dendritic cell/tumor fusions following autologous stem cell transplant induces immunologic and clinical responses in multiple myeloma patients. Clin. Cancer Res. 2013, 19, 3640–3648. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ogasawara, M.; Miyashita, M.; Yamagishi, Y.; Ota, S. Phase I/II Pilot Study of Wilms’ Tumor 1 Peptide-Pulsed Dendritic Cell Vaccination Combined With Conventional Chemotherapy in Patients With Head and Neck Cancer. Ther. Apher. Dial. 2019, 23, 279–288. [Google Scholar] [CrossRef]
- Tanyi, J.L.; Bobisse, S.; Ophir, E.; Tuyaerts, S.; Roberti, A.; Genolet, R.; Baumgartner, P.; Stevenson, B.J.; Iseli, C.; Dangaj, D.; et al. Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer. Sci. Transl. Med. 2018, 10, eaao5931. [Google Scholar] [CrossRef] [Green Version]
- Alard, E.; Butnariu, A.B.; Grillo, M.; Kirkham, C.; Zinovkin, D.A.; Newnham, L.; Macciochi, J.; Pranjol, M.Z.I. Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets. Cancers 2020, 12, 1826. [Google Scholar] [CrossRef]
- Lopes, A.; Vandermeulen, G.; Preat, V. Cancer DNA vaccines: Current preclinical and clinical developments and future perspectives. J. Exp. Clin. Cancer Res. 2019, 38, 146. [Google Scholar] [CrossRef] [PubMed]
- Calmeiro, J.; Carrascal, M.A.; Tavares, A.R.; Ferreira, D.A.; Gomes, C.; Falcao, A.; Cruz, M.T.; Neves, B.M. Dendritic Cell Vaccines for Cancer Immunotherapy: The Role of Human Conventional Type 1 Dendritic Cells. Pharmaceutics 2020, 12, 158. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ziani, L.; Chouaib, S.; Thiery, J. Alteration of the Antitumor Immune Response by Cancer-Associated Fibroblasts. Front. Immunol. 2018, 9, 414. [Google Scholar] [CrossRef] [PubMed]
- Mantovani, A.; Marchesi, F.; Malesci, A.; Laghi, L.; Allavena, P. Tumour-associated macrophages as treatment targets in oncology. Nat. Rev. Clin. Oncol. 2017, 14, 399–416. [Google Scholar] [CrossRef]
- Kuen, J.; Darowski, D.; Kluge, T.; Majety, M. Pancreatic cancer cell/fibroblast co-culture induces M2 like macrophages that influence therapeutic response in a 3D model. PLoS ONE 2017, 12, e0182039. [Google Scholar] [CrossRef] [PubMed]
- Chiarugi, P. Cancer-associated fibroblasts and macrophages: Friendly conspirators for malignancy. Oncoimmunology 2013, 2, e25563. [Google Scholar] [CrossRef] [Green Version]
- Fujii, N.; Shomori, K.; Shiomi, T.; Nakabayashi, M.; Takeda, C.; Ryoke, K.; Ito, H. Cancer-associated fibroblasts and CD163-positive macrophages in oral squamous cell carcinoma: Their clinicopathological and prognostic significance. J. Oral. Pathol. Med. 2012, 41, 444–451. [Google Scholar] [CrossRef] [PubMed]
- Herrera, M.; Herrera, A.; Dominguez, G.; Silva, J.; Garcia, V.; Garcia, J.M.; Gomez, I.; Soldevilla, B.; Munoz, C.; Provencio, M.; et al. Cancer-associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients. Cancer Sci. 2013, 104, 437–444. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ocana, A.; Nieto-Jimenez, C.; Pandiella, A.; Templeton, A.J. Neutrophils in cancer: Prognostic role and therapeutic strategies. Mol. Cancer 2017, 16, 137. [Google Scholar] [CrossRef] [Green Version]
- Powell, D.R.; Huttenlocher, A. Neutrophils in the Tumor Microenvironment. Trends Immunol. 2016, 37, 41–52. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shaul, M.E.; Fridlender, Z.G. Neutrophils as active regulators of the immune system in the tumor microenvironment. J. Leukoc. Biol. 2017, 102, 343–349. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Giraldo, N.A.; Becht, E.; Remark, R.; Damotte, D.; Sautes-Fridman, C.; Fridman, W.H. The immune contexture of primary and metastatic human tumours. Curr. Opin. Immunol. 2014, 27, 8–15. [Google Scholar] [CrossRef] [PubMed]
- Wu, Y.; Tian, Z.; Wei, H. Developmental and Functional Control of Natural Killer Cells by Cytokines. Front. Immunol. 2017, 8, 930. [Google Scholar] [CrossRef] [PubMed]
- Balsamo, M.; Scordamaglia, F.; Pietra, G.; Manzini, C.; Cantoni, C.; Boitano, M.; Queirolo, P.; Vermi, W.; Facchetti, F.; Moretta, A.; et al. Melanoma-associated fibroblasts modulate NK cell phenotype and antitumor cytotoxicity. Proc. Natl. Acad. Sci. USA 2009, 106, 20847–20852. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, T.; Yang, Y.; Hua, X.; Wang, G.; Liu, W.; Jia, C.; Tai, Y.; Zhang, Q.; Chen, G. Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO. Cancer Lett. 2012, 318, 154–161. [Google Scholar] [CrossRef]
- Li, T.; Yi, S.; Liu, W.; Jia, C.; Wang, G.; Hua, X.; Tai, Y.; Zhang, Q.; Chen, G. Colorectal carcinoma-derived fibroblasts modulate natural killer cell phenotype and antitumor cytotoxicity. Med. Oncol. 2013, 30, 663. [Google Scholar] [CrossRef]
- Malchiodi, Z.X.; Weiner, L.M. Understanding and Targeting Natural Killer Cell-Cancer-Associated Fibroblast Interactions in Pancreatic Ductal Adenocarcinoma. Cancers 2021, 13, 405. [Google Scholar] [CrossRef] [PubMed]
- Sanjabi, S.; Mosaheb, M.M.; Flavell, R.A. Opposing effects of TGF-beta and IL-15 cytokines control the number of short-lived effector CD8+ T cells. Immunity 2009, 31, 131–144. [Google Scholar] [CrossRef] [Green Version]
- Ahmadzadeh, M.; Rosenberg, S.A. TGF-beta 1 attenuates the acquisition and expression of effector function by tumor antigen-specific human memory CD8 T cells. J. Immunol. 2005, 174, 5215–5223. [Google Scholar] [CrossRef] [Green Version]
- Thomas, D.A.; Massague, J. TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell 2005, 8, 369–380. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Feig, C.; Jones, J.O.; Kraman, M.; Wells, R.J.; Deonarine, A.; Chan, D.S.; Connell, C.M.; Roberts, E.W.; Zhao, Q.; Caballero, O.L.; et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc. Natl. Acad. Sci. USA 2013, 110, 20212–20217. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Erez, N.; Truitt, M.; Olson, P.; Arron, S.T.; Hanahan, D. Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner. Cancer Cell 2010, 17, 135–147. [Google Scholar] [CrossRef] [Green Version]
- Kim, H.J.; Cantor, H. CD4 T-cell subsets and tumor immunity: The helpful and the not-so-helpful. Cancer Immunol. Res. 2014, 2, 91–98. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barnas, J.L.; Simpson-Abelson, M.R.; Brooks, S.P.; Kelleher, R.J., Jr.; Bankert, R.B. Reciprocal functional modulation of the activation of T lymphocytes and fibroblasts derived from human solid tumors. J. Immunol. 2010, 185, 2681–2692. [Google Scholar] [CrossRef] [PubMed]
- Haniffa, M.A.; Wang, X.N.; Holtick, U.; Rae, M.; Isaacs, J.D.; Dickinson, A.M.; Hilkens, C.M.; Collin, M.P. Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cells. J. Immunol. 2007, 179, 1595–1604. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liao, D.; Luo, Y.; Markowitz, D.; Xiang, R.; Reisfeld, R.A. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PLoS ONE 2009, 4, e7965. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stromnes, I.M.; Schmitt, T.M.; Hulbert, A.; Brockenbrough, J.S.; Nguyen, H.; Cuevas, C.; Dotson, A.M.; Tan, X.; Hotes, J.L.; Greenberg, P.D.; et al. T Cells Engineered against a Native Antigen Can Surmount Immunologic and Physical Barriers to Treat Pancreatic Ductal Adenocarcinoma. Cancer Cell 2015, 28, 638–652. [Google Scholar] [CrossRef] [Green Version]
- Hartmann, N.; Giese, N.A.; Giese, T.; Poschke, I.; Offringa, R.; Werner, J.; Ryschich, E. Prevailing role of contact guidance in intrastromal T-cell trapping in human pancreatic cancer. Clin. Cancer Res. 2014, 20, 3422–3433. [Google Scholar] [CrossRef] [Green Version]
- Jiang, H.; Hegde, S.; Knolhoff, B.L.; Zhu, Y.; Herndon, J.M.; Meyer, M.A.; Nywening, T.M.; Hawkins, W.G.; Shapiro, I.M.; Weaver, D.T.; et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat. Med. 2016, 22, 851–860. [Google Scholar] [CrossRef] [PubMed]
- Salmon, H.; Franciszkiewicz, K.; Damotte, D.; Dieu-Nosjean, M.C.; Validire, P.; Trautmann, A.; Mami-Chouaib, F.; Donnadieu, E. Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors. J. Clin. Investig. 2012, 122, 899–910. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mildner, A.; Jung, S. Development and function of dendritic cell subsets. Immunity 2014, 40, 642–656. [Google Scholar] [CrossRef] [Green Version]
- Flavell, R.A.; Sanjabi, S.; Wrzesinski, S.H.; Licona-Limon, P. The polarization of immune cells in the tumour environment by TGFbeta. Nat. Rev. Immunol. 2010, 10, 554–567. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Raker, V.K.; Domogalla, M.P.; Steinbrink, K. Tolerogenic Dendritic Cells for Regulatory T Cell Induction in Man. Front. Immunol. 2015, 6, 569. [Google Scholar] [CrossRef] [Green Version]
- Travis, M.A.; Sheppard, D. TGF-beta activation and function in immunity. Annu. Rev. Immunol. 2014, 32, 51–82. [Google Scholar] [CrossRef] [Green Version]
- Dikov, M.M.; Ohm, J.E.; Ray, N.; Tchekneva, E.E.; Burlison, J.; Moghanaki, D.; Nadaf, S.; Carbone, D.P. Differential roles of vascular endothelial growth factor receptors 1 and 2 in dendritic cell differentiation. J. Immunol. 2005, 174, 215–222. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gabrilovich, D.; Ishida, T.; Oyama, T.; Ran, S.; Kravtsov, V.; Nadaf, S.; Carbone, D.P. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 1998, 92, 4150–4166. [Google Scholar] [CrossRef]
- Gabrilovich, D.I.; Chen, H.L.; Girgis, K.R.; Cunningham, H.T.; Meny, G.M.; Nadaf, S.; Kavanaugh, D.; Carbone, D.P. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat. Med. 1996, 2, 1096–1103. [Google Scholar] [CrossRef] [PubMed]
- Oyama, T.; Ran, S.; Ishida, T.; Nadaf, S.; Kerr, L.; Carbone, D.P.; Gabrilovich, D.I. Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. J. Immunol. 1998, 160, 1224–1232. [Google Scholar] [PubMed]
- Gabrilovich, D.I.; Nagaraj, S. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 2009, 9, 162–174. [Google Scholar] [CrossRef] [PubMed]
- Kumar, V.; Patel, S.; Tcyganov, E.; Gabrilovich, D.I. The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment. Trends Immunol. 2016, 37, 208–220. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, J.H.; Oh, S.H.; Kim, E.J.; Park, S.J.; Hong, S.P.; Cheon, J.H.; Kim, T.I.; Kim, W.H. The role of myofibroblasts in upregulation of S100A8 and S100A9 and the differentiation of myeloid cells in the colorectal cancer microenvironment. Biochem. Biophys. Res. Commun. 2012, 423, 60–66. [Google Scholar] [CrossRef] [PubMed]
- Mace, T.A.; Ameen, Z.; Collins, A.; Wojcik, S.; Mair, M.; Young, G.S.; Fuchs, J.R.; Eubank, T.D.; Frankel, W.L.; Bekaii-Saab, T.; et al. Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner. Cancer Res. 2013, 73, 3007–3018. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, X.; Lin, Y.; Shi, Y.; Li, B.; Liu, W.; Yin, W.; Dang, Y.; Chu, Y.; Fan, J.; He, R. FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3-CCL2 Signaling. Cancer Res. 2016, 76, 4124–4135. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barnas, J.L.; Simpson-Abelson, M.R.; Yokota, S.J.; Kelleher, R.J.; Bankert, R.B. T cells and stromal fibroblasts in human tumor microenvironments represent potential therapeutic targets. Cancer Microenviron. 2010, 3, 29–47. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ford, K.; Hanley, C.J.; Mellone, M.; Szyndralewiez, C.; Heitz, F.; Wiesel, P.; Wood, O.; Machado, M.; Lopez, M.A.; Ganesan, A.P.; et al. NOX4 Inhibition Potentiates Immunotherapy by Overcoming Cancer-Associated Fibroblast-Mediated CD8 T-cell Exclusion from Tumors. Cancer Res. 2020, 80, 1846–1860. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ene-Obong, A.; Clear, A.J.; Watt, J.; Wang, J.; Fatah, R.; Riches, J.C.; Marshall, J.F.; Chin-Aleong, J.; Chelala, C.; Gribben, J.G.; et al. Activated pancreatic stellate cells sequester CD8+ T cells to reduce their infiltration of the juxtatumoral compartment of pancreatic ductal adenocarcinoma. Gastroenterology 2013, 145, 1121–1132. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cho, Y.A.; Yoon, H.J.; Lee, J.I.; Hong, S.P.; Hong, S.D. Relationship between the expressions of PD-L1 and tumor-infiltrating lymphocytes in oral squamous cell carcinoma. Oral. Oncol. 2011, 47, 1148–1153. [Google Scholar] [CrossRef]
- Nazareth, M.R.; Broderick, L.; Simpson-Abelson, M.R.; Kelleher, R.J., Jr.; Yokota, S.J.; Bankert, R.B. Characterization of human lung tumor-associated fibroblasts and their ability to modulate the activation of tumor-associated T cells. J. Immunol. 2007, 178, 5552–5562. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pinchuk, I.V.; Saada, J.I.; Beswick, E.J.; Boya, G.; Qiu, S.M.; Mifflin, R.C.; Raju, G.S.; Reyes, V.E.; Powell, D.W. PD-1 ligand expression by human colonic myofibroblasts/fibroblasts regulates CD4+ T-cell activity. Gastroenterology 2008, 135, 1228–1237. [Google Scholar] [CrossRef] [Green Version]
- Li, Z.; Zhou, J.; Zhang, J.; Li, S.; Wang, H.; Du, J. Cancer-associated fibroblasts promote PD-L1 expression in mice cancer cells via secreting CXCL5. Int. J. Cancer 2019, 145, 1946–1957. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yu, P.F.; Huang, Y.; Han, Y.Y.; Lin, L.Y.; Sun, W.H.; Rabson, A.B.; Wang, Y.; Shi, Y.F. TNFalpha-activated mesenchymal stromal cells promote breast cancer metastasis by recruiting CXCR2(+) neutrophils. Oncogene 2017, 36, 482–490. [Google Scholar] [CrossRef] [PubMed]
- Scanlan, M.J.; Raj, B.K.; Calvo, B.; Garin-Chesa, P.; Sanz-Moncasi, M.P.; Healey, J.H.; Old, L.J.; Rettig, W.J. Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers. Proc. Natl. Acad. Sci. USA 1994, 91, 5657–5661. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cohen, S.J.; Alpaugh, R.K.; Palazzo, I.; Meropol, N.J.; Rogatko, A.; Xu, Z.; Hoffman, J.P.; Weiner, L.M.; Cheng, J.D. Fibroblast activation protein and its relationship to clinical outcome in pancreatic adenocarcinoma. Pancreas 2008, 37, 154–158. [Google Scholar] [CrossRef] [PubMed]
- Goscinski, M.A.; Suo, Z.; Florenes, V.A.; Vlatkovic, L.; Nesland, J.M.; Giercksky, K.E. FAP-alpha and uPA show different expression patterns in premalignant and malignant esophageal lesions. Ultrastruct. Pathol. 2008, 32, 89–96. [Google Scholar] [CrossRef] [PubMed]
- Henry, L.R.; Lee, H.O.; Lee, J.S.; Klein-Szanto, A.; Watts, P.; Ross, E.A.; Chen, W.T.; Cheng, J.D. Clinical implications of fibroblast activation protein in patients with colon cancer. Clin. Cancer. Res. 2007, 13, 1736–1741. [Google Scholar] [CrossRef] [Green Version]
- Garin-Chesa, P.; Old, L.J.; Rettig, W.J. Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. Proc. Natl. Acad. Sci. USA 1990, 87, 7235–7239. [Google Scholar] [CrossRef] [Green Version]
- Shi, M.; Yu, D.H.; Chen, Y.; Zhao, C.Y.; Zhang, J.; Liu, Q.H.; Ni, C.R.; Zhu, M.H. Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance. World J. Gastroenterol. 2012, 18, 840–846. [Google Scholar] [CrossRef]
- Cheng, J.D.; Dunbrack, R.L., Jr.; Valianou, M.; Rogatko, A.; Alpaugh, R.K.; Weiner, L.M. Promotion of tumor growth by murine fibroblast activation protein, a serine protease, in an animal model. Cancer Res. 2002, 62, 4767–4772. [Google Scholar]
- Kraman, M.; Bambrough, P.J.; Arnold, J.N.; Roberts, E.W.; Magiera, L.; Jones, J.O.; Gopinathan, A.; Tuveson, D.A.; Fearon, D.T. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science 2010, 330, 827–830. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wong, P.F.; Wei, W.; Gupta, S.; Smithy, J.W.; Zelterman, D.; Kluger, H.M.; Rimm, D.L. Multiplex quantitative analysis of cancer-associated fibroblasts and immunotherapy outcome in metastatic melanoma. J. Immunother. Cancer 2019, 7, 194. [Google Scholar] [CrossRef] [Green Version]
- Wen, Y.; Wang, C.T.; Ma, T.T.; Li, Z.Y.; Zhou, L.N.; Mu, B.; Leng, F.; Shi, H.S.; Li, Y.O.; Wei, Y.Q. Immunotherapy targeting fibroblast activation protein inhibits tumor growth and increases survival in a murine colon cancer model. Cancer Sci. 2010, 101, 2325–2332. [Google Scholar] [CrossRef] [PubMed]
- Ostermann, E.; Garin-Chesa, P.; Heider, K.H.; Kalat, M.; Lamche, H.; Puri, C.; Kerjaschki, D.; Rettig, W.J.; Adolf, G.R. Effective immunoconjugate therapy in cancer models targeting a serine protease of tumor fibroblasts. Clin. Cancer Res. 2008, 14, 4584–4592. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, H.; Wu, Q.; Liu, Z.; Luo, X.; Fan, Y.; Liu, Y.; Zhang, Y.; Hua, S.; Fu, Q.; Zhao, M.; et al. Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma. Cell Death Dis. 2014, 5, e1155. [Google Scholar] [CrossRef] [PubMed]
- Santos, A.M.; Jung, J.; Aziz, N.; Kissil, J.L.; Pure, E. Targeting fibroblast activation protein inhibits tumor stromagenesis and growth in mice. J. Clin. Investig. 2009, 119, 3613–3625. [Google Scholar] [CrossRef] [PubMed]
- Adams, S.; Miller, G.T.; Jesson, M.I.; Watanabe, T.; Jones, B.; Wallner, B.P. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004, 64, 5471–5480. [Google Scholar] [CrossRef] [Green Version]
- LeBeau, A.M.; Brennen, W.N.; Aggarwal, S.; Denmeade, S.R. Targeting the cancer stroma with a fibroblast activation protein-activated promelittin protoxin. Mol. Cancer Ther. 2009, 8, 1378–1386. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Scott, A.M.; Wiseman, G.; Welt, S.; Adjei, A.; Lee, F.T.; Hopkins, W.; Divgi, C.R.; Hanson, L.H.; Mitchell, P.; Gansen, D.N.; et al. A Phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer. Clin. Cancer Res. 2003, 9, 1639–1647. [Google Scholar]
- Hofheinz, R.D.; al-Batran, S.E.; Hartmann, F.; Hartung, G.; Jager, D.; Renner, C.; Tanswell, P.; Kunz, U.; Amelsberg, A.; Kuthan, H.; et al. Stromal antigen targeting by a humanised monoclonal antibody: An early phase II trial of sibrotuzumab in patients with metastatic colorectal cancer. Onkologie 2003, 26, 44–48. [Google Scholar] [CrossRef] [PubMed]
- Narra, K.; Mullins, S.R.; Lee, H.O.; Strzemkowski-Brun, B.; Magalong, K.; Christiansen, V.J.; McKee, P.A.; Egleston, B.; Cohen, S.J.; Weiner, L.M.; et al. Phase II trial of single agent Val-boroPro (Talabostat) inhibiting Fibroblast Activation Protein in patients with metastatic colorectal cancer. Cancer Biol. Ther. 2007, 6, 1691–1699. [Google Scholar] [CrossRef] [Green Version]
- Pickup, M.W.; Mouw, J.K.; Weaver, V.M. The extracellular matrix modulates the hallmarks of cancer. EMBO Rep. 2014, 15, 1243–1253. [Google Scholar] [CrossRef] [Green Version]
- Calon, A.; Lonardo, E.; Berenguer-Llergo, A.; Espinet, E.; Hernando-Momblona, X.; Iglesias, M.; Sevillano, M.; Palomo-Ponce, S.; Tauriello, D.V.; Byrom, D.; et al. Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat. Genet. 2015, 47, 320–329. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chakravarthy, A.; Khan, L.; Bensler, N.P.; Bose, P.; De Carvalho, D.D. TGF-beta-associated extracellular matrix genes link cancer-associated fibroblasts to immune evasion and immunotherapy failure. Nat. Commun. 2018, 9, 4692. [Google Scholar] [CrossRef] [PubMed]
- Lan, Y.; Zhang, D.; Xu, C.; Hance, K.W.; Marelli, B.; Qi, J.; Yu, H.; Qin, G.; Sircar, A.; Hernandez, V.M.; et al. Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein simultaneously targeting PD-L1 and TGF-beta. Sci. Transl. Med. 2018, 10, eaan5448. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tauriello, D.V.F.; Palomo-Ponce, S.; Stork, D.; Berenguer-Llergo, A.; Badia-Ramentol, J.; Iglesias, M.; Sevillano, M.; Ibiza, S.; Canellas, A.; Hernando-Momblona, X.; et al. TGFbeta drives immune evasion in genetically reconstituted colon cancer metastasis. Nature 2018, 554, 538–543. [Google Scholar] [CrossRef] [Green Version]
- Kieffer, Y.; Hocine, H.R.; Gentric, G.; Pelon, F.; Bernard, C.; Bourachot, B.; Lameiras, S.; Albergante, L.; Bonneau, C.; Guyard, A.; et al. Single-Cell Analysis Reveals Fibroblast Clusters Linked to Immunotherapy Resistance in Cancer. Cancer Discov. 2020, 10, 1330–1351. [Google Scholar] [CrossRef] [PubMed]
- Zhao, F.; Evans, K.; Xiao, C.; DeVito, N.; Theivanthiran, B.; Holtzhausen, A.; Siska, P.J.; Blobe, G.C.; Hanks, B.A. Stromal Fibroblasts Mediate Anti-PD-1 Resistance via MMP-9 and Dictate TGFbeta Inhibitor Sequencing in Melanoma. Cancer Immunol. Res. 2018, 6, 1459–1471. [Google Scholar] [CrossRef] [PubMed]
- Ohshio, Y.; Teramoto, K.; Hanaoka, J.; Tezuka, N.; Itoh, Y.; Asai, T.; Daigo, Y.; Ogasawara, K. Cancer-associated fibroblast-targeted strategy enhances antitumor immune responses in dendritic cell-based vaccine. Cancer Sci. 2015, 106, 134–142. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.; Fassnacht, M.; Nair, S.; Boczkowski, D.; Gilboa, E. Tumor immunotherapy targeting fibroblast activation protein, a product expressed in tumor-associated fibroblasts. Cancer Res. 2005, 65, 11156–11163. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Loeffler, M.; Kruger, J.A.; Niethammer, A.G.; Reisfeld, R.A. Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake. J. Clin. Investig. 2006, 116, 1955–1962. [Google Scholar] [CrossRef] [Green Version]
- Fassnacht, M.; Lee, J.; Milazzo, C.; Boczkowski, D.; Su, Z.; Nair, S.; Gilboa, E. Induction of CD4(+) and CD8(+) T-cell responses to the human stromal antigen, fibroblast activation protein: Implication for cancer immunotherapy. Clin. Cancer Res. 2005, 11, 5566–5571. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.; Ertl, H.C. Depletion of FAP+ cells reduces immunosuppressive cells and improves metabolism and functions CD8+T cells within tumors. Oncotarget 2016, 7, 23282–23299. [Google Scholar] [CrossRef] [Green Version]
- Geng, F.; Bao, X.; Dong, L.; Guo, Q.Q.; Guo, J.; Xie, Y.; Zhou, Y.; Yu, B.; Wu, H.; Wu, J.X.; et al. Doxorubicin pretreatment enhances FAPalpha/survivin co-targeting DNA vaccine anti-tumor activity primarily through decreasing peripheral MDSCs in the 4T1 murine breast cancer model. Oncoimmunology 2020, 9, 1747350. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fakhrai, H.; Dorigo, O.; Shawler, D.L.; Lin, H.; Mercola, D.; Black, K.L.; Royston, I.; Sobol, R.E. Eradication of established intracranial rat gliomas by transforming growth factor beta antisense gene therapy. Proc. Natl. Acad. Sci. USA 1996, 93, 2909–2914. [Google Scholar] [CrossRef] [Green Version]
- Nemunaitis, J.; Dillman, R.O.; Schwarzenberger, P.O.; Senzer, N.; Cunningham, C.; Cutler, J.; Tong, A.; Kumar, P.; Pappen, B.; Hamilton, C.; et al. Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer. J. Clin. Oncol. 2006, 24, 4721–4730. [Google Scholar] [CrossRef] [PubMed]
- Nemunaitis, J.; Nemunaitis, M.; Senzer, N.; Snitz, P.; Bedell, C.; Kumar, P.; Pappen, B.; Maples, P.B.; Shawler, D.; Fakhrai, H. Phase II trial of Belagenpumatucel-L, a TGF-beta2 antisense gene modified allogeneic tumor vaccine in advanced non small cell lung cancer (NSCLC) patients. Cancer Gene Ther. 2009, 16, 620–624. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Giaccone, G.; Bazhenova, L.A.; Nemunaitis, J.; Tan, M.; Juhasz, E.; Ramlau, R.; van den Heuvel, M.M.; Lal, R.; Kloecker, G.H.; Eaton, K.D.; et al. A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer. Eur. J. Cancer 2015, 51, 2321–2329. [Google Scholar] [CrossRef] [Green Version]
- Bhowmick, N.A.; Neilson, E.G.; Moses, H.L. Stromal fibroblasts in cancer initiation and progression. Nature 2004, 432, 332–337. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.C.; Lo, A.; Scholler, J.; Sun, J.; Majumdar, R.S.; Kapoor, V.; Antzis, M.; Cotner, C.E.; Johnson, L.A.; Durham, A.C.; et al. Targeting fibroblast activation protein in tumor stroma with chimeric antigen receptor T cells can inhibit tumor growth and augment host immunity without severe toxicity. Cancer Immunol. Res. 2014, 2, 154–166. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tran, E.; Chinnasamy, D.; Yu, Z.; Morgan, R.A.; Lee, C.C.; Restifo, N.P.; Rosenberg, S.A. Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia. J. Exp. Med. 2013, 210, 1125–1135. [Google Scholar] [CrossRef] [PubMed]
- Lee, P.P.; Yee, C.; Savage, P.A.; Fong, L.; Brockstedt, D.; Weber, J.S.; Johnson, D.; Swetter, S.; Thompson, J.; Greenberg, P.D.; et al. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat. Med. 1999, 5, 677–685. [Google Scholar] [CrossRef] [PubMed]
- Kakarla, S.; Chow, K.K.; Mata, M.; Shaffer, D.R.; Song, X.T.; Wu, M.F.; Liu, H.; Wang, L.L.; Rowley, D.R.; Pfizenmaier, K.; et al. Antitumor effects of chimeric receptor engineered human T cells directed to tumor stroma. Mol. Ther. 2013, 21, 1611–1620. [Google Scholar] [CrossRef] [PubMed]
- Schuberth, P.C.; Hagedorn, C.; Jensen, S.M.; Gulati, P.; van den Broek, M.; Mischo, A.; Soltermann, A.; Jungel, A.; Marroquin Belaunzaran, O.; Stahel, R.; et al. Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific re-directed T cells. J. Transl. Med. 2013, 11, 187. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lo, A.; Wang, L.S.; Scholler, J.; Monslow, J.; Avery, D.; Newick, K.; O’Brien, S.; Evans, R.A.; Bajor, D.J.; Clendenin, C.; et al. Tumor-Promoting Desmoplasia Is Disrupted by Depleting FAP-Expressing Stromal Cells. Cancer Res. 2015, 75, 2800–2810. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Akhurst, R.J. TGF-beta antagonists: Why suppress a tumor suppressor? J. Clin. Investig. 2002, 109, 1533–1536. [Google Scholar] [CrossRef] [PubMed]
- Akhurst, R.J. TGF beta signaling in health and disease. Nat. Genet. 2004, 36, 790–792. [Google Scholar] [CrossRef] [PubMed]
- Bollard, C.M.; Rossig, C.; Calonge, M.J.; Huls, M.H.; Wagner, H.J.; Massague, J.; Brenner, M.K.; Heslop, H.E.; Rooney, C.M. Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity. Blood 2002, 99, 3179–3187. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kloss, C.C.; Lee, J.; Zhang, A.; Chen, F.; Melenhorst, J.J.; Lacey, S.F.; Maus, M.V.; Fraietta, J.A.; Zhao, Y.; June, C.H. Dominant-Negative TGF-beta Receptor Enhances PSMA-Targeted Human CAR T Cell Proliferation And Augments Prostate Cancer Eradication. Mol. Ther. 2018, 26, 1855–1866. [Google Scholar] [CrossRef] [Green Version]
- Bollard, C.M.; Tripic, T.; Cruz, C.R.; Dotti, G.; Gottschalk, S.; Torrano, V.; Dakhova, O.; Carrum, G.; Ramos, C.A.; Liu, H.; et al. Tumor-Specific T-Cells Engineered to Overcome Tumor Immune Evasion Induce Clinical Responses in Patients With Relapsed Hodgkin Lymphoma. J. Clin. Oncol. 2018, 36, 1128–1139. [Google Scholar] [CrossRef]
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Sliker, B.H.; Campbell, P.M. Fibroblasts Influence the Efficacy, Resistance, and Future Use of Vaccines and Immunotherapy in Cancer Treatment. Vaccines 2021, 9, 634. https://doi.org/10.3390/vaccines9060634
Sliker BH, Campbell PM. Fibroblasts Influence the Efficacy, Resistance, and Future Use of Vaccines and Immunotherapy in Cancer Treatment. Vaccines. 2021; 9(6):634. https://doi.org/10.3390/vaccines9060634
Chicago/Turabian StyleSliker, Bailee H., and Paul M. Campbell. 2021. "Fibroblasts Influence the Efficacy, Resistance, and Future Use of Vaccines and Immunotherapy in Cancer Treatment" Vaccines 9, no. 6: 634. https://doi.org/10.3390/vaccines9060634