TIGIT Can Exert Immunosuppressive Effects on CD8+ T Cells by the CD155/TIGIT Signaling Pathway for Hepatocellular Carcinoma In Vitro.

The efficacy of adoptive cellular immunotherapy against cancer cells is limited due to the presence of immunosuppressive cells within the solid tumor microenvironment. The upregulation of certain coinhibitory receptors may lead to exhaustion of the immune effector cells. T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an immune inhibitory receptor expressed by regulatory T cells and activated T cells and natural killer cells. The aim of this study was to determine the immunosuppressive effects of CD155/TIGIT signaling on CD8(+)T cells of adoptive cellular immunotherapy in hepatocellular carcinoma (HCC). Our studies found that CD155 was overexpressed in HCC, and CD155(hi)HCC cells upregulated TIGIT on CD8(+)T cells, which decreased the secretion of interferon-gamma, tumor necrosis factor-alpha, and interleukin-17A and increased that of interleukin-10 from the effector cells. However, TIGIT blockade or CD155-knockdown reversed the inhibitory effect of HCC cells on CD8(+)T-cell effector function. These results indicate that TIGIT can exert an immunosuppressive effect on CD8 T cells by modulating cytokine production through CD155, and is a promising target to optimize adoptive cellular immunotherapy against HCC.