Clinical Perspectives to Overcome Acquired Resistance to Anti-Programmed Death-1 and Anti-Programmed Death Ligand-1 Therapy in Non-Small Cell Lung Cancer |
Lee, Yong Jun
(Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine)
Lee, Jii Bum (Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine) Ha, Sang-Jun (Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University) Kim, Hye Ryun (Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine) |
1 | Zingg, D., Arenas-Ramirez, N., Sahin, D., Rosalia, R.A., Antunes, A.T., Haeusel, J., Sommer, L., and Boyman, O. (2017). The histone methyltransferase Ezh2 controls mechanisms of adaptive resistance to tumor immunotherapy. Cell Rep. 20, 854-867. DOI |
2 | Genova, C., Boccardo, S., Mora, M., Rijavec, E., Biello, F., Rossi, G., Tagliamento, M., Dal Bello, M.G., Coco, S., Alama, A., et al. (2019). Correlation between B7-H4 and survival of non-small-cell lung cancer patients treated with nivolumab. J. Clin. Med. 8, 1566. DOI |
3 | Hou, A., Hou, K., Huang, Q., Lei, Y., and Chen, W. (2020). Targeting myeloid-derived suppressor cell, a promising strategy to overcome resistance to immune checkpoint inhibitors. Front. Immunol. 11, 783. DOI |
4 | Mazzone, R., Zwergel, C., Mai, A., and Valente, S. (2017). Epi-drugs in combination with immunotherapy: a new avenue to improve anticancer efficacy. Clin. Epigenetics 9, 59. DOI |
5 | Mahoney, K.M., Rennert, P.D., and Freeman, G.J. (2015). Combination cancer immunotherapy and new immunomodulatory targets. Nat. Rev. Drug Discov. 14, 561-584. DOI |
6 | Manguso, R.T., Pope, H.W., Zimmer, M.D., Brown, F.D., Yates, K.B., Miller, B.C., Collins, N.B., Bi, K., LaFleur, M.W., Juneja, V.R., et al. (2017). In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature 547, 413-418. DOI |
7 | Mariathasan, S., Turley, S.J., Nickles, D., Castiglioni, A., Yuen, K., Wang, Y., Kadel, E.E., III, Koeppen, H., Astarita, J.L., Cubas, R., et al. (2018). TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 554, 544-548. DOI |
8 | Alfaro, C., Teijeira, A., Onate, C., Perez, G., Sanmamed, M.F., Andueza, M.P., Alignani, D., Labiano, S., Azpilikueta, A., Rodriguez-Paulete, A., et al. (2016). Tumor-produced interleukin-8 attracts human myeloid-derived suppressor cells and elicits extrusion of neutrophil extracellular traps (NETs). Clin. Cancer Res. 22, 3924-3936. DOI |
9 | Meder, L., Schuldt, P., Thelen, M., Schmitt, A., Dietlein, F., Klein, S., Borchmann, S., Wennhold, K., Vlasic, I., Oberbeck, S., et al. (2018). Combined VEGF and PD-L1 blockade displays synergistic treatment effects in an autochthonous mouse model of small cell lung cancer. Cancer Res. 78, 4270-4281. DOI |
10 | Abiko, K., Matsumura, N., Hamanishi, J., Horikawa, N., Murakami, R., Yamaguchi, K., Yoshioka, Y., Baba, T., Konishi, I., and Mandai, M. (2015). IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. Br. J. Cancer 112, 1501-1509. DOI |
11 | Baxter, E., Windloch, K., Gannon, F., and Lee, J.S. (2014). Epigenetic regulation in cancer progression. Cell Biosci. 4, 45. DOI |
12 | Rodriguez-Abreu, D., Johnson, M.L., Hussein, M.A., Cobo, M., Patel, A.J., Secen, N.M., Lee, K.H., Massuti, B., Hiret, S., Yang, J.C.H., et al. (2020). Primary analysis of a randomized, double-blind, phase II study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE). J. Clin. Oncol. 38(15 Suppl), 9503. DOI |
13 | Thommen, D.S., Schreiner, J., Muller, P., Herzig, P., Roller, A., Belousov, A., Umana, P., Pisa, P., Klein, C., Bacac, M., et al. (2015). Progression of lung cancer is associated with increased dysfunction of T cells defined by coexpression of multiple inhibitory receptors. Cancer Immunol. Res. 3, 1344-1355. DOI |
14 | Xu, L.J., Ma, Q., Zhu, J., Li, J., Xue, B.X., Gao, J., Sun, C.Y., Zang, Y.C., Zhou, Y.B., Yang, D.R., et al. (2018). Combined inhibition of JAK1, 2/Stat3-PD-L1 signaling pathway suppresses the immune escape of castration-resistant prostate cancer to NK cells in hypoxia. Mol. Med. Rep. 17, 8111-8120. |
15 | Arlauckas, S.P., Garris, C.S., Kohler, R.H., Kitaoka, M., Cuccarese, M.F., Yang, K.S., Miller, M.A., Carlson, J.C., Freeman, G.J., Anthony, R.M., et al. (2017). In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy. Sci. Transl. Med. 9, eaal3604. DOI |
16 | Bach, E.A., Aguet, M., and Schreiber, R.D. (1997). The IFNγ receptor: a paradigm for cytokine receptor signaling. Annu. Rev. Immunol. 15, 563-591. DOI |
17 | Chanmee, T., Ontong, P., Konno, K., and Itano, N. (2014). Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel) 6, 1670-1690. DOI |
18 | Arenas-Ramirez, N., Sahin, D., and Boyman, O. (2018). Epigenetic mechanisms of tumor resistance to immunotherapy. Cell. Mol. Life Sci. 75, 4163-4176. DOI |
19 | Meyer, C., Cagnon, L., Costa-Nunes, C.M., Baumgaertner, P., Montandon, N., Leyvraz, L., Michielin, O., Romano, E., and Speiser, D.E. (2014). Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol. Immunother. 63, 247-257. DOI |
20 | Zhu, Y., Knolhoff, B.L., Meyer, M.A., Nywening, T.M., West, B.L., Luo, J., Wang-Gillam, A., Goedegebuure, S.P., Linehan, D.C., and DeNardo, D.G. (2014). CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res. 74, 5057-5069. DOI |
21 | Miao, D., Margolis, C.A., Gao, W., Voss, M.H., Li, W., Martini, D.J., Norton, C., Bosse, D., Wankowicz, S.M., Cullen, D., et al. (2018). Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science 359, 801-806. DOI |
22 | Neel, J.C., Humbert, L., and Lebrun, J.J. (2012). The dual role of TGFβ in human cancer: from tumor suppression to cancer metastasis. ISRN Mol. Biol. 2012, 381428. DOI |
23 | Pereira, C., Gimenez-Xavier, P., Pros, E., Pajares, M.J., Moro, M., Gomez, A., Navarro, A., Condom, E., Moran, S., Gomez-Lopez, G., et al. (2017). Genomic profiling of patient-derived xenografts for lung cancer identifies B2M inactivation impairing immunorecognition. Clin. Cancer Res. 23, 3203-3213. DOI |
24 | Bagchi, S., Yuan, R., and Engleman, E.G. (2021). Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance. Annu. Rev. Pathol. 16, 223-249. DOI |
25 | Pauken, K.E., Sammons, M.A., Odorizzi, P.M., Manne, S., Godec, J., Khan, O., Drake, A.M., Chen, Z., Sen, D.R., Kurachi, M., et al. (2016). Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science 354, 1160-1165. DOI |
26 | Peng, W., Chen, J.Q., Liu, C., Malu, S., Creasy, C., Tetzlaff, M.T., Xu, C., McKenzie, J.A., Zhang, C., Liang, X., et al. (2016). Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 6, 202-216. DOI |
27 | Fong, L., Forde, P.M., Powderly, J.D., Goldman, J.W., Nemunaitis, J.J., Luke, J.J., Hellmann, M.D., Kummar, S., Doebele, R.C., Mahadevan, D., et al. (2017). Safety and clinical activity of adenosine A2a receptor (A2aR) antagonist, CPI-444, in anti-PD1/PDL1 treatment-refractory renal cell (RCC) and non-small cell lung cancer (NSCLC) patients. J. Clin. Oncol. 35(15 Suppl), 3004. |
28 | Galon, J. and Bruni, D. (2019). Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat. Rev. Drug Discov. 18, 197-218. DOI |
29 | Garcia-Diaz, A., Shin, D.S., Moreno, B.H., Saco, J., Escuin-Ordinas, H., Rodriguez, G.A., Zaretsky, J.M., Sun, L., Hugo, W., Wang, X., et al. (2017). Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. Cell Rep. 19, 1189-1201. DOI |
30 | Ettinger, D.S., Wood, D.E., Aggarwal, C., Aisner, D.L., Akerley, W., Bauman, J.R., Bharat, A., Bruno, D.S., Chang, J.Y., Chirieac, L.R., et al. (2019). NCCN guidelines insights: non-small cell lung cancer, version 1.2020: featured updates to the NCCN guidelines. J. Natl. Compr. Canc. Netw. 17, 1464-1472. DOI |
31 | Pourmir, I., Gazeau, B., de Saint Basile, H., and Fabre, E. (2020). Biomarkers of resistance to immune checkpoint inhibitors in non-small-cell lung cancer: myth or reality? Cancer Drug Resist. 3, 276-286. |
32 | Pan, D., Kobayashi, A., Jiang, P., Ferrari de Andrade, L., Tay, R.E., Luoma, A.M., Tsoucas, D., Qiu, X., Lim, K., Rao, P., et al. (2018). A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing. Science 359, 770-775. DOI |
33 | Ribas, A., Shin, D.S., Zaretsky, J., Frederiksen, J., Cornish, A., Avramis, E., Seja, E., Kivork, C., Siebert, J., Kaplan-Lefko, P., et al. (2016). PD-1 blockade expands intratumoral memory T cells. Cancer Immunol. Res. 4, 194-203. DOI |
34 | Gettinger, S., Choi, J., Hastings, K., Truini, A., Datar, I., Sowell, R., Wurtz, A., Dong, W., Cai, G., Melnick, M.A., et al. (2017). Impaired HLA class I antigen processing and presentation as a mechanism of acquired resistance to immune checkpoint inhibitors in lung cancer. Cancer Discov. 7, 1420-1435. DOI |
35 | Hanks, B.A., Holtzhausen, A., Evans, K., Heid, M., and Blobe, G.C. (2014). Combinatorial TGF-β signaling blockade and anti-CTLA-4 antibody immunotherapy in a murine BRAFV600E-PTEN-/- transgenic model of melanoma. J. Clin. Oncol. 32(15 Suppl), 3011. DOI |
36 | Hellmann, M.D., Friedman, C.F., and Wolchok, J.D. (2016). Combinatorial cancer immunotherapies. Adv. Immunol. 130, 251-277. DOI |
37 | Mok, T.S.K., Wu, Y.L., Kudaba, I., Kowalski, D.M., Cho, B.C., Turna, H.Z., Castro, G., Jr., Srimuninnimit, V., Laktionov, K.K., Bondarenko, I., et al. (2019). Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 393, 1819-1830. DOI |
38 | Platten, M., von Knebel Doeberitz, N., Oezen, I., Wick, W., and Ochs, K. (2015). Cancer immunotherapy by targeting IDO1/TDO and their downstream effectors. Front. Immunol. 5, 673. DOI |
39 | Remon, J., Passiglia, F., Ahn, M.J., Barlesi, F., Forde, P.M., Garon, E.B., Gettinger, S., Goldberg, S.B., Herbst, R.S., Horn, L., et al. (2020). Immune checkpoint inhibitors in thoracic malignancies: review of the existing evidence by an IASLC expert panel and recommendations. J. Thorac. Oncol. 15, 914-947. DOI |
40 | Ren, D., Hua, Y., Yu, B., Ye, X., He, Z., Li, C., Wang, J., Mo, Y., Wei, X., Chen, Y., et al. (2020). Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy. Mol. Cancer 19, 19. DOI |
41 | Sharma, P., Hu-Lieskovan, S., Wargo, J.A., and Ribas, A. (2017). Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 168, 707-723. DOI |
42 | 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. (2015). TIGIT and PD-1 impair tumor antigen-specific CD8+ T cells in melanoma patients. J. Clin. Invest. 125, 2046-2058. DOI |
43 | Chen, P.L., Roh, W., Reuben, A., Cooper, Z.A., Spencer, C.N., Prieto, P.A., Miller, J.P., Bassett, R.L., Gopalakrishnan, V., Wani, K., et al. (2016). Analysis of immune signatures in longitudinal tumor samples yields insight into biomarkers of response and mechanisms of resistance to immune checkpoint blockade. Cancer Discov. 6, 827-837. DOI |
44 | Kim, D., Lee, Y.S., Kim, D.H., and Bae, S.C. (2020). Lung cancer staging and associated genetic and epigenetic events. Mol. Cells 43, 1-9. DOI |
45 | Ricciuti, B., Leonardi, G.C., Puccetti, P., Fallarino, F., Bianconi, V., Sahebkar, A., Baglivo, S., Chiari, R., and Pirro, M. (2019). Targeting indoleamine-2, 3-dioxygenase in cancer: scientific rationale and clinical evidence. Pharmacol. Ther. 196, 105-116. DOI |
46 | Saleh, R. and Elkord, E. (2019). Treg-mediated acquired resistance to immune checkpoint inhibitors. Cancer Lett. 457, 168-179. DOI |
47 | Shin, D.S., Zaretsky, J.M., Escuin-Ordinas, H., Garcia-Diaz, A., Hu-Lieskovan, S., Kalbasi, A., Grasso, C.S., Hugo, W., Sandoval, S., Torrejon, D.Y., et al. (2017). Primary resistance to PD-1 blockade mediated by JAK1/2 mutations. Cancer Discov. 7, 188-201. DOI |
48 | Socinski, M.A., Jotte, R.M., Cappuzzo, F., Orlandi, F., Stroyakovskiy, D., Nogami, N., Rodriguez-Abreu, D., Moro-Sibilot, D., Thomas, C.A., Barlesi, F., et al. (2018). Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N. Engl. J. Med. 378, 2288-2301. DOI |
49 | Hu-Lieskovan, S. and Ribas, A. (2017). New combination strategies using PD-1/L1 checkpoint inhibitors as a backbone. Cancer J. 23, 10-22. DOI |
50 | Koyama, S., Akbay, E.A., Li, Y.Y., Herter-Sprie, G.S., Buczkowski, K.A., Richards, W.G., Gandhi, L., Redig, A.J., Rodig, S.J., Asahina, H., et al. (2016). Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat. Commun. 7, 10501. DOI |
51 | Jenkins, R.W., Barbie, D.A., and Flaherty, K.T. (2018). Mechanisms of resistance to immune checkpoint inhibitors. Br. J. Cancer 118, 9-16. DOI |
52 | Kanwal, R. and Gupta, S. (2012). Epigenetic modifications in cancer. Clin. Genet. 81, 303-311. DOI |
53 | Young, A., Ngiow, S.F., Gao, Y., Patch, A.M., Barkauskas, D.S., Messaoudene, M., Lin, G., Coudert, J.D., Stannard, K.A., Zitvogel, L., et al. (2018). A2AR adenosine signaling suppresses natural killer cell maturation in the tumor microenvironment. Cancer Res. 78, 1003-1016. DOI |
54 | Su, T., Zhang, Y., Valerie, K., Wang, X.Y., Lin, S., and Zhu, G. (2019). STING activation in cancer immunotherapy. Theranostics 9, 7759-7771. DOI |
55 | Spranger, S., Koblish, H.K., Horton, B., Scherle, P.A., Newton, R., and Gajewski, T.F. (2014). Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8+ T cells directly within the tumor microenvironment. J. Immunother. Cancer 2, 3. DOI |
56 | Stanley, E.R. and Chitu, V. (2014). CSF-1 receptor signaling in myeloid cells. Cold Spring Harb. Perspect. Biol. 6, a021857. DOI |
57 | Steven, A., Fisher, S.A., and Robinson, B.W. (2016). Immunotherapy for lung cancer. Respirology 21, 821-833. DOI |
58 | Sucker, A., Zhao, F., Pieper, N., Heeke, C., Maltaner, R., Stadtler, N., Real, B., Bielefeld, N., Howe, S., Weide, B., et al. (2017). Acquired IFNγ resistance impairs anti-tumor immunity and gives rise to T-cell-resistant melanoma lesions. Nat. Commun. 8, 15440. DOI |
59 | Sucker, A., Zhao, F., Real, B., Heeke, C., Bielefeld, N., Maβen, S., Horn, S., Moll, I., Maltaner, R., Horn, P.A., et al. (2014). Genetic evolution of T-cell resistance in the course of melanoma progression. Clin. Cancer Res. 20, 6593-6604. DOI |
60 | 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. (2012). Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci. Transl. Med. 4, 127ra37. DOI |
61 | Toor, S.M., Nair, V.S., Decock, J., and Elkord, E. (2020). Immune checkpoints in the tumor microenvironment. Semin. Cancer Biol. 65, 1-12. DOI |
62 | Toso, A., Revandkar, A., Di Mitri, D., Guccini, I., Proietti, M., Sarti, M., Pinton, S., Zhang, J., Kalathur, M., Civenni, G., et al. (2014). Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity. Cell Rep. 9, 75-89. DOI |
63 | Vanpouille-Box, C., Diamond, J.M., Pilones, K.A., Zavadil, J., Babb, J.S., Formenti, S.C., Barcellos-Hoff, M.H., and Demaria, S. (2015). TGFβ is a master regulator of radiation therapy-induced antitumor immunity. Cancer Res. 75, 2232-2242. DOI |
64 | Vijayan, D., Young, A., Teng, M.W., and Smyth, M.J. (2017). Targeting immunosuppressive adenosine in cancer. Nat. Rev. Cancer 17, 709-724. DOI |
65 | Voron, T., Colussi, O., Marcheteau, E., Pernot, S., Nizard, M., Pointet, A.L., Latreche, S., Bergaya, S., Benhamouda, N., Tanchot, C., et al. (2015). VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J. Exp. Med. 212, 139-148. DOI |
66 | Wang, F., Wang, S., and Zhou, Q. (2020). The resistance mechanisms of lung cancer immunotherapy. Front. Oncol. 10, 568059. DOI |
67 | Yamaguchi, H. and Hung, M.C. (2014). Regulation and role of EZH2 in cancer. Cancer Res. Treat. 46, 209-222. DOI |
68 | Yuen, K.C., Liu, L.F., Gupta, V., Madireddi, S., Keerthivasan, S., Li, C., Rishipathak, D., Williams, P., Kadel, E.E., 3rd, Koeppen, H., et al. (2020). High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade. Nat. Med. 26, 693-698. DOI |
69 | Zaretsky, J.M., Garcia-Diaz, A., Shin, D.S., Escuin-Ordinas, H., Hugo, W., Hu-Lieskovan, S., Torrejon, D.Y., Abril-Rodriguez, G., Sandoval, S., Barthly, L., et al. (2016). Mutations associated with acquired resistance to PD-1 blockade in melanoma. N. Engl. J. Med. 375, 819-829. DOI |
70 | Topalian, S.L., Drake, C.G., and Pardoll, D.M. (2015). Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 27, 450-461. DOI |
71 | Zang, X., Loke, P., Kim, J., Murphy, K., Waitz, R., and Allison, J.P. (2003). B7x: a widely expressed B7 family member that inhibits t cell activation. Proc. Natl. Acad. Sci. U. S. A. 100, 10388-10392. DOI |
72 | Zauderer, M.G., Szlosarek, P.W., Le Moulec, S., Popat, S., Taylor, P., Planchard, D., Scherpereel, A., Jahan, T.M., Koczywas, M., Forster, M., et al. (2020). Safety and efficacy of tazemetostat, an enhancer of zeste-homolog 2 inhibitor, in patients with relapsed or refractory malignant mesothelioma. J. Clin. Oncol. 38(15 Suppl), 9058. DOI |
73 | Zhang, H., Conrad, D.M., Butler, J.J., Zhao, C., Blay, J., and Hoskin, D.W. (2004). Adenosine acts through A2 receptors to inhibit IL-2-induced tyrosine phosphorylation of STAT5 in T lymphocytes: role of cyclic adenosine 3', 5'-monophosphate and phosphatases. J. Immunol. 173, 932-944. DOI |
74 | Sakaguchi, S., Yamaguchi, T., Nomura, T., and Ono, M. (2008). Regulatory T cells and immune tolerance. Cell 133, 775-787. DOI |
75 | Ashizawa, T., Iizuka, A., Maeda, C., Tanaka, E., Kondou, R., Miyata, H., Sugino, T., Kawata, T., Deguchi, S., Mitsuya, K., et al. (2019). Impact of combination therapy with anti-PD-1 blockade and a STAT3 inhibitor on the tumor-infiltrating lymphocyte status. Immunol. Lett. 216, 43-50. DOI |