The T-cell surface molecule TIGIT is an immune checkpoint molecule that inhibits T-cell responses, but its roles in cancer are little understood. In this study, we evaluated the role TIGIT checkpoint plays in the development and progression of gastric cancer. We show that the percentage of CD8 T cells that are TIGIT þ was increased in gastric cancer patients compared with healthy individuals. These cells showed functional exhaustion with impaired activation, proliferation, cytokine production, and metabolism, all of which were rescued by glucose. In addition, gastric cancer tissue and cell lines expressed CD155, which bound TIGIT receptors and inactivated CD8 T cells. In a T cell-gastric cancer cell coculture system, gastric cancer cells deprived CD8 T cells of glucose and impaired CD8 T-cell effector functions; these effects were neutralized by the additional glucose or by TIGIT blockade. In gastric cancer tumor cells, CD155 silencing increased T-cell metabolism and IFNg production, whereas CD155 overexpression inhibited T-cell metabolism and IFNg production; this inhibition was neutralized by TIGIT blockade. Targeting CD155/TIGIT enhanced CD8 T-cell reaction and improved survival in tumor-bearing mice. Combined targeting of TIGIT and PD-1 further enhanced CD8 T-cell activation and improved survival in tumor-bearing mice.Our results suggest that gastric cancer cells inhibit CD8 T-cell metabolism through CD155/TIGIT signaling, which inhibits CD8 T-cell effector functions, resulting in hyporesponsive antitumor immunity. These findings support the candidacy of CD155/TIGIT as a potential therapeutic target in gastric cancer.

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As a transmembrane enzyme, ATP synthase plays an important role in energy metabolism of organ tissues, as well as in tumors. In this study we generated a monoclonal antibody, 6G11, to the catalytic subunit of F1-F0 ATP synthase (ATP5B). The SDS-PAGE result demonstrated that the hybridoma clone had a molecular weight of 50 and 27 kDa components that could be the heavy and light chains of the monoclonal antibody, respectively. Chromosome analysis of the hybridoma clone proved that they had 98 to 102 chromosomal numbers that were the sum of the SP2/0 and spleen cells. Western blot assay revealed that the hybridoma clone reacted specifically with the ATP synthase beta subunit, but not with other proteins. In addition, the subclass of the hybridoma clone was identified as IgG1 by capture ELISA. Furthermore, it demonstrated that the antibody retained stability after half a year. These results indicated that the hybridoma clone 6G11 was a monoclonal antibody with significant stability and special reactivity to ATP5B antigen.