TIGIT in cancer immunotherapy
Tóm tắt
Tumors evade immune-mediated recognition through multiple mechanisms of immune escape. On chronic tumor antigen exposure, T cells become dysfunctional/exhausted and upregulate various checkpoint inhibitory receptors (IRs) that limit T cells’ survival and function. During the last decade, immunotherapies targeting IRs such as programmed cell death receptor 1 (PD-1) and anticytotoxic T lymphocyte-associated antigen 4 (CTLA-4) have provided ample evidence of clinical benefits in many solid tumors. Beyond CTLA-4 and PD-1, multiple other IRs are also targeted with immune checkpoint blockade in the clinic. Specifically, T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is a promising new target for cancer immunotherapy. TIGIT is upregulated by immune cells, including activated T cells, natural killer cells, and regulatory T cells. TIGIT binds to two ligands, CD155 (PVR) and CD112 (PVRL2, nectin-2), that are expressed by tumor cells and antigen-presenting cells in the tumor microenvironment. There is now ample evidence that the TIGIT pathway regulates T cell-mediated and natural killer cell-mediated tumor recognition in vivo and in vitro. Dual PD-1/TIGIT blockade potently increases tumor antigen-specific CD8+ T cell expansion and function in vitro and promotes tumor rejection in mouse tumor models. These findings support development of ongoing clinical trials with dual PD-1/TIGIT blockade in patients with cancer.
Từ khóa
Tài liệu tham khảo
Topalian, 2019, Five-Year survival and correlates among patients with advanced melanoma, renal cell carcinoma, or Non–Small cell lung cancer treated with nivolumab, JAMA Oncol, 5, 10.1001/jamaoncol.2019.2187
Hamid, 2019, Five-Year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001, Ann Oncol, 30, 582, 10.1093/annonc/mdz011
Fourcade, 2018, Cd226 opposes TIGIT to disrupt Tregs in melanoma, JCI Insight, 3, 10.1172/jci.insight.121157
Kim, 2017, Cd226-/- natural killer cells fail to establish stable contacts with cancer cells and show impaired control of tumor metastasis in vivo, Oncoimmunology, 6, 10.1080/2162402X.2017.1338994
Wang, 2018, Combination cancer immunotherapy targeting PD-1 and GITR can rescue CD8+ T cell dysfunction and maintain memory phenotype, Sci Immunol, 3, 10.1126/sciimmunol.aat7061
Lepletier, 2020, Tumor CD155 expression is associated with resistance to anti-PD1 immunotherapy in metastatic melanoma, Clin Cancer Res, 26, clincanres.3925.2019, 10.1158/1078-0432.CCR-19-3925
Rodriguez-Abreu, 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), JCO, 38, 9503, 10.1200/JCO.2020.38.15_suppl.9503
Xu, 2017, Blockade of CD112R and TIGIT signaling sensitizes human natural killer cell functions, Cancer Immunol Immunother, 66, 1367, 10.1007/s00262-017-2031-x
Chiang, 2020, CD96 functions as a co-stimulatory receptor to enhance CD8+ T cell activation and effector responses, Eur J Immunol, 50, 891, 10.1002/eji.201948405
Chen, 2019, FcγR-Binding is an important functional attribute for immune checkpoint antibodies in cancer immunotherapy, Front Immunol, 10
Waight, 2018, Selective FcγR Co-engagement on APCs Modulates the Activity of Therapeutic Antibodies Targeting T Cell Antigens, Cancer Cell, 33, 1033, 10.1016/j.ccell.2018.05.005