CD155/TIGIT signaling regulates the effector function of tumor-infiltrating CD8(+) T cell by NF-kappa B pathway in colorectal cancer

Background and Aim: CD155/T-cell inununoglobulin and ITIM domain (TIGIT) suppressed anti-cancer immunity in several cancers, but its roles in colorectal cancer (CRC) were not clear. Here, we investigated its roles in CRC. Methods: The percentages of CD8(+) T cells expressing TIGIT and secreting cytokines (IL-2, TNF-alpha, and IFN gamma) were evaluated by flow cytometry. The expression level of CD155 was determined by western blot and inununohistochemistry. The levels of cytokines were determined by enzyme-linked immunosorbent assay. The activation of the nuclear factor-kappa B (NF-kappa B) pathway was examined by western blot and immunofluorescent assay. Results: T-cell immunoglobulin and ITIM domain was overexpressed on CD8(+) T cells of CRC patients and mice. CD155 was overexpressed in mice CRC tissues and cells. The addition of CD155 recombinant protein could decrease the percentages of CD8(+) T cells secreting cytokines. Blocking TIGIT could increase the percentages of cytokine-secreting CD8(+) T cells. Coculturing with CD155-knockdown CRC cells could upregulate the percentages of CD8(+) T cells secreting cytokines. Blocking TIGIT partially counteracted the effect of the knockdown of CD155. Besides, coculturing with CD155-knockdown CRC cells could promote the secretion of cytokines, activate the NF-kappa B pathway, and enhance the nuclear translocation of p65. And these effects were counteracted by the application of an NF-kappa B inhibitor. Finally, blocking TIGIT played anti-cancer roles such as suppression of tumor growth, increasing the percentages of cytokine-secreting CD8(+) T cells and activation of the NF-kappa B signaling pathway. Conclusion: Suppressing CD155/TIGIT exerted anti-cancer effects against CRC, and our findings provided a potential therapeutic approach to treat CRC.