From T cell “exhaustion” to anti-cancer immunity

Grégory Verdeil1, Silvia A. Fuertes Marraco1, Timothy Murray1, Daniel E. Speiser1
1Ludwig Cancer Research Center and Department of Oncology, Clinical Tumor Biology & Immunotherapy Group, Lausanne University Hospital Center (CHUV) and University of Lausanne, Route de la Corniche 9A, CH-1066 Epalinges, Switzerland

Tài liệu tham khảo

Fearon, 2001, Arrested differentiation, the self-renewing memory lymphocyte, and vaccination, Science (N. Y.), 293, 248, 10.1126/science.1062589 Zanetti, 2010, Memory T cells, Pref. Adv. Exp. Med. Biol., 684, vii Zhang, 2011, CD8(+) T cells: foot soldiers of the immune system, Immunity, 35, 161, 10.1016/j.immuni.2011.07.010 Gattinoni, 2012, Paths to stemness: building the ultimate antitumour T cell, Nat. Rev. Cancer, 12, 671, 10.1038/nrc3322 Graef, 2014, Serial transfer of single-cell-derived immunocompetence reveals stemness of CD8(+) central memory T cells, Immunity, 41, 116, 10.1016/j.immuni.2014.05.018 Fuertes Marraco, 2015, Long-lasting stem cell-like memory CD8+ T cells with a naïve-like profile upon yellow fever vaccination, Sci. Transl. Med., 7, 282ra48, 10.1126/scitranslmed.aaa3700 D.W. MD, 2013, Best practice & research clinical haematology, Best Pract. Res. Clin. Haematol., 26, 293 Vyas, 2015, Biology of blood and marrow transplantation, Biol. Blood Marrow Transplant., 21, 8, 10.1016/j.bbmt.2014.10.026 Walunas, 1994, CTLA-4 can function as a negative regulator of T cell activation, Immunity, 1, 405, 10.1016/1074-7613(94)90071-X Krummel, 1995, CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation, J. Exp. Med., 182, 459, 10.1084/jem.182.2.459 Waterhouse, 1995, Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4, Science (N. Y.), 270, 985, 10.1126/science.270.5238.985 Tivol, 1995, Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4, Immunity, 3, 541, 10.1016/1074-7613(95)90125-6 Leach, 1996, Enhancement of antitumor immunity by CTLA-4 blockade, Science (N. Y.), 271, 1734, 10.1126/science.271.5256.1734 Callahan, 2013, At the bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy, J. Leukoc. Biol., 94, 41, 10.1189/jlb.1212631 Hodi, 2010, Improved survival with ipilimumab in patients with metastatic melanoma, N. Engl. J. Med., 363, 711, 10.1056/NEJMoa1003466 Robert, 2011, Ipilimumab plus dacarbazine for previously untreated metastatic melanoma, N. Engl. J. Med., 364, 2517, 10.1056/NEJMoa1104621 Schadendorf, 2015, Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma, J. Clin. Oncol., 10.1200/JCO.2014.56.2736 Keir, 2008, PD-1 and its ligands in tolerance and immunity, Annu. Rev. Immunol., 26, 677, 10.1146/annurev.immunol.26.021607.090331 Taube, 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, 10.1126/scitranslmed.3003689 Iwai, 2002, Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade, Proc. Natl. Acad. Sci. U. S. A., 99, 12293, 10.1073/pnas.192461099 Dong, 2002, Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion, Nat. Med., 8, 793, 10.1038/nm730 Robert, 2015, Pembrolizumab versus ipilimumab in advanced melanoma, N. Engl. J. Med., 10.1056/NEJMoa1503093 Topalian, 2012, Safety, activity, and immune correlates of anti-PD-1 antibody in cancer, N. Engl. J. Med., 366, 2443, 10.1056/NEJMoa1200690 Garon, 2015, Pembrolizumab for the treatment of non-small-cell lung cancer, N. Engl. J. Med., 10.1056/NEJMoa1501824 Callahan, 2014, CTLA-4 and PD-1 pathway blockade: combinations in the clinic, Front. Oncol., 4, 385 Naidoo, 2014, Immune modulation for cancer therapy, Br. J. Cancer, 10.1038/bjc.2014.348 Shin, 2015, The evolution of checkpoint blockade as a cancer therapy: what's here, what's next?, Curr. Opin. Immunol., 33, 23, 10.1016/j.coi.2015.01.006 Wolchok, 2013, Nivolumab plus ipilimumab in advanced melanoma, N. Engl. J. Med., 369, 122, 10.1056/NEJMoa1302369 Speiser, 2002, In vivo activation of melanoma-specific CD8(+) T cells by endogenous tumor antigen and peptide vaccines. A comparison to virus-specific T cells, Eur. J. Immunol., 32, 731, 10.1002/1521-4141(200203)32:3<731::AID-IMMU731>3.0.CO;2-H Haanen, 2006, Melanoma-specific tumor-infiltrating lymphocytes but not circulating melanoma-specific T cells may predict survival in resected advanced-stage melanoma patients, Cancer Immunol. Immunother., 55, 451, 10.1007/s00262-005-0018-5 Fridman, 2012, The immune contexture in human tumours: impact on clinical outcome, Nat. Rev. Cancer, 12, 298, 10.1038/nrc3245 Gerlinger, 2012, Intratumor heterogeneity and branched evolution revealed by multiregion sequencing, N. Engl. J. Med., 366, 883, 10.1056/NEJMoa1113205 Romano, 2013, Identification of multiple mechanisms of resistance to vemurafenib in a patient with BRAFV600E-mutated cutaneous melanoma successfully rechallenged after progression, Clin. Cancer Res., 19, 5749, 10.1158/1078-0432.CCR-13-0661 Schumacher, 2015, Neoantigens in cancer immunotherapy, Science (N. Y.), 348, 69, 10.1126/science.aaa4971 Gubin, 2014, Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens, Nature, 515, 577, 10.1038/nature13988 Yadav, 2014, Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing, Nature, 515, 572, 10.1038/nature14001 Herbst, 2014, Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients, Nature, 515, 563, 10.1038/nature14011 Linnemann, 2015, High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma, Nat. Med., 21, 81, 10.1038/nm.3773 Rizvi, 2015, Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer, Science (N. Y.), 348, 124, 10.1126/science.aaa1348 Baitsch, 2012, The three main stumbling blocks for anticancer T cells, Trends Immunol., 33, 364, 10.1016/j.it.2012.02.006 Allavena, 2012, Immunology in the clinic review series; focus on cancer: tumour-associated macrophages: undisputed stars of the inflammatory tumour microenvironment, Clin. Exp. Immunol., 167, 195, 10.1111/j.1365-2249.2011.04515.x Gabrilovich, 2012, Coordinated regulation of myeloid cells by tumours, Nat. Rev. Immunol., 12, 253, 10.1038/nri3175 Devaud, 2013, Immune modulation of the tumor microenvironment for enhancing cancer immunotherapy, OncoImmunology, 2, e25961, 10.4161/onci.25961 Swartz, 2014, Immunomodulatory roles of lymphatic vessels in cancer progression, Cancer Immunol. Res., 2, 701, 10.1158/2326-6066.CIR-14-0115 Vignali, 2008, How regulatory T cells work, Nat. Rev. Immunol., 8, 523, 10.1038/nri2343 Ostrand-Rosenberg, 2009, Myeloid-derived suppressor cells: linking inflammation and cancer, J. Immunol., 182, 4499, 10.4049/jimmunol.0802740 Ostman, 2009, Cancer-associated fibroblasts and tumor growth—bystanders turning into key players, Curr. Opin. Genet. Dev., 19, 67, 10.1016/j.gde.2009.01.003 Blackburn, 2009, Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection, Nat. Immunol., 10, 29, 10.1038/ni.1679 Wherry, 2007, Molecular signature of CD8+ T cell exhaustion during chronic viral infection, Immunity, 27, 670, 10.1016/j.immuni.2007.09.006 Wherry, 2004, Antigen-independent memory CD8 T cells do not develop during chronic viral infection, Proc. Natl. Acad. Sci. U. S. A., 101, 16004, 10.1073/pnas.0407192101 Day, 2006, PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression, Nature, 443, 350, 10.1038/nature05115 Quigley, 2010, Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF, Nat. Med., 16, 1147, 10.1038/nm.2232 Larsson, 2013, Molecular signatures of T-cell inhibition in HIV-1 infection, Retrovirology, 10, 31, 10.1186/1742-4690-10-31 Baitsch, 2011, Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients, J. Clin. Invest., 121, 2350, 10.1172/JCI46102 Fourcade, 2012, CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1, Cancer Res., 72, 887, 10.1158/0008-5472.CAN-11-2637 Zippelius, 2004, Effector function of human tumor-specific CD8 T cells in melanoma lesions: a state of local functional tolerance, Cancer Res., 64, 2865, 10.1158/0008-5472.CAN-03-3066 Legat, 2013, Inhibitory receptor expression depends more dominantly on differentiation and activation than “exhaustion” of human CD8 T Cells, Front. Immunol., 4, 455, 10.3389/fimmu.2013.00455 Radvanyi, 2012, Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients, Clin. Cancer Res., 18, 6758, 10.1158/1078-0432.CCR-12-1177 Gros, 2014, PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors, J. Clin. Invest., 124, 2246, 10.1172/JCI73639 Pentcheva-Hoang, 2004, B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse, Immunity, 21, 401, 10.1016/j.immuni.2004.06.017 Nirschl, 2013, Molecular pathways: coexpression of immune checkpoint molecules: signaling pathways and implications for cancer immunotherapy, Clin. Cancer Res., 19, 4917, 10.1158/1078-0432.CCR-12-1972 Rangachari, 2012, Bat3 promotes T cell responses and autoimmunity by repressing Tim-3-mediated cell death and exhaustion, Nat. Med., 18, 1394, 10.1038/nm.2871 Huang, 2015, CEACAM1 regulates TIM-3-mediated tolerance and exhaustion, Nature, 517, 386, 10.1038/nature13848 Derré, 2010, BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination, J. Clin. Invest., 120, 157, 10.1172/JCI40070 Johnston, 2014, The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function, Cancer Cell, 26, 923, 10.1016/j.ccell.2014.10.018 Yu, 2008, The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells, Nat. Immunol., 10, 48, 10.1038/ni.1674 Workman, 2002, Cutting edge: molecular analysis of the negative regulatory function of lymphocyte activation gene-3, J. Immunol., 169, 5392, 10.4049/jimmunol.169.10.5392 Peggs, 2009, Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies, J. Exp. Med., 206, 1717, 10.1084/jem.20082492 Takahashi, 2000, Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4, J. Exp. Med., 192, 303, 10.1084/jem.192.2.303 Read, 2000, Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation, J. Exp. Med., 192, 295, 10.1084/jem.192.2.295 Walker, 2011, The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses, Nat. Rev. Immunol., 11, 852, 10.1038/nri3108 Das, 2015, Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo, J. Immunol., 194, 950, 10.4049/jimmunol.1401686 Grosso, 2013, CTLA-4 blockade in tumor models: an overview of preclinical and translational research, Cancer Immun., 13, 5 Vazquez-Cintron, 2010, Tumor-induced disruption of proximal TCR-mediated signal transduction in tumor-infiltrating CD8+ lymphocytes inactivates antitumor effector phase, J. Immunol., 185, 7133, 10.4049/jimmunol.1001157 Kyi, 2013, Checkpoint blocking antibodies in cancer immunotherapy, FEBS Lett., 588, 368, 10.1016/j.febslet.2013.10.015 Nguyen, 2015, Clinical blockade of PD1 and LAG3—potential mechanisms of action, Nat. Rev. Immunol., 15, 45, 10.1038/nri3790 Doering, 2012, Network analysis reveals centrally connected genes and pathways involved in CD8, Immunity, 37, 1130, 10.1016/j.immuni.2012.08.021 Crawford, 2014, Molecular and transcriptional basis of CD4+ T cell dysfunction during chronic infection, Immunity, 40, 289, 10.1016/j.immuni.2014.01.005 Crespo, 2013, T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment, Curr. Opin. Immunol., 25, 214, 10.1016/j.coi.2012.12.003 Parish, 2009, The molecular signature of CD8+ T cells undergoing deletional tolerance, Blood, 113, 4575, 10.1182/blood-2008-10-185223 Macián, 2002, Transcriptional mechanisms underlying lymphocyte tolerance, Cell, 109, 719, 10.1016/S0092-8674(02)00767-5 Shin, 2009, A role for the transcriptional repressor blimp-1 in CD8(+) T cell exhaustion during chronic viral infection, Immunity, 31, 309, 10.1016/j.immuni.2009.06.019 Martinez, 2015, The transcription factor NFAT promotes exhaustion of activated CD8, Immunity, 42, 265, 10.1016/j.immuni.2015.01.006 Intlekofer, 2005, Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin, Nat. Immunol., 6, 1236, 10.1038/ni1268 Angelosanto, 2010, Transcription factor regulation of CD8+ T-cell memory and exhaustion, Immunol. Rev., 236, 167, 10.1111/j.1600-065X.2010.00927.x Best, 2013, Transcriptional insights into the CD8+ T cell response to infection and memory T cell formation, Nat. Immunol., 14, 404, 10.1038/ni.2536 Grange, 2013, Active STAT5 regulates T-bet and eomesodermin expression in CD8 T cells and imprints a T-bet-dependent Tc1 program with repressed IL-6/TGF-β1 signaling, J. Immunol., 191, 3712, 10.4049/jimmunol.1300319 Curran, 2013, Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of eomesodermin, J. Exp. Med., 210, 743, 10.1084/jem.20121190 Paley, 2012, Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection, Science (N. Y.), 338, 1220, 10.1126/science.1229620 Buggert, 2014, T-bet and eomes are differentially linked to the exhausted phenotype of CD8+ T cells in HIV infection, PLoS Pathog., 10, e1004251, 10.1371/journal.ppat.1004251 Berrien-Elliott, 2015, Checkpoint blockade immunotherapy relies on T-bet but not eomes to induce effector function in tumor-infiltrating CD8+ T cells, Cancer Immunol. Res., 3, 116, 10.1158/2326-6066.CIR-14-0159 Doedens, 2013, Hypoxia-inducible factors enhance the effector responses of CD8(+) T cells to persistent antigen, Nat. Immunol., 14, 1173, 10.1038/ni.2714 Stephen, 2014, Transforming growth factor beta-mediated suppression of antitumor T cells requires FoxP1 transcription factor expression, Immunity, 41, 427, 10.1016/j.immuni.2014.08.012 Uyttenhove, 2003, Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase, Nat. Med., 9, 1269, 10.1038/nm934 Frumento, 2002, Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase, J. Exp. Med., 196, 459, 10.1084/jem.20020121 Opitz, 2011, An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor, Nature, 478, 197, 10.1038/nature10491 Ling, 2014, Mesenchymal stem cells use IDO to regulate immunity in tumor microenvironment, Cancer Res., 74, 1576, 10.1158/0008-5472.CAN-13-1656 Winans, 2015, Linking the aryl hydrocarbon receptor with altered DNA methylation patterns and developmentally induced aberrant antiviral CD8+ T cell responses, J. Immunol., 194, 4446, 10.4049/jimmunol.1402044 Mascanfroni, 2015, Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1α, Nat. Med., 10.1038/nm.3868 Huijbers, 2006, An inducible mouse model of melanoma expressing a defined tumor antigen, Cancer Res., 66, 3278, 10.1158/0008-5472.CAN-05-3216 Soudja, 2010, Tumor-initiated inflammation overrides protective adaptive immunity in an induced melanoma model in mice, Cancer Res., 70, 3515, 10.1158/0008-5472.CAN-09-4354 Giordano, 2014, The tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) imposes a brake on antitumor activity of CD8 T cells, Proc. Natl. Acad. Sci. U. S. A., 111, 11115, 10.1073/pnas.1406259111 Zhou, 2014, In vivo discovery of immunotherapy targets in the tumour microenvironment, Nature, 506, 52, 10.1038/nature12988 Utzschneider, 2013, T cells maintain an exhausted phenotype after antigen withdrawal and population reexpansion, Nat. Immunol., 14, 603, 10.1038/ni.2606 Speiser, 2014, T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?, Nat. Rev. Immunol., 14, 768, 10.1038/nri3740 Galluzzi, 2014, Classification of current anticancer immunotherapies, Oncotarget, 5, 12472, 10.18632/oncotarget.2998