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TIGIT in cancer 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.

  • costimulatory and inhibitory T-cell receptors
  • immunotherapy
  • therapies
  • investigational

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