期刊
JOURNAL FOR IMMUNOTHERAPY OF CANCER
卷 8, 期 2, 页码 -出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/jitc-2020-000957
关键词
costimulatory and inhibitory T-cell receptors; immunotherapy; therapies; investigational
资金
- NIH/NCI [R01CA228181, R01CA222203]
- Bristol-Myers Squibb
- cancer vaccine collaborative clinical strategy team grant
- NCI [P50CA121973]
- James W and Frances G McGlothlin Chair in Melanoma Immunotherapy
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.
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