Identification Of Co‐inhibitory Receptor Expression On T Cells From Gastric Cancerpatients

The critical role of tumour antigen-specific immune responses to restrain tumourgrowth in patients with gastric cancer furthers the need to dissect the co-inhibitorypathways involved in tumour infiltrating lymphocyte (TIL) exhaustion/dysfunction. Itwas previously reported that PD-1expression was significantly increased on CD4+andCD8+T cells from patients with gastric cancer and in gastric cancer tissues, comparedto normal donors. Using Flow Cytometry, we observed up-regulation of TIM-3andPD-1expression on peripheral T cells and up-regulation of CTLA-4, TIGIT, TIM-3and PD-1expression on TILs from gastric cancer patients; however TIGIT wasdown-regulated on CD8+TILs and TIM-3up-regulation on CD8+TILs was notstatistically significant. Furthermore, the percentages of PD-1+/TIM-3+andPD-1+/TIM-3-peripheral T cells was significantly higher in gastric cancer patients thannormal donors, and the percentage of PD-1+/TIM-3+TILs was significantly higher thanthe percentage of PD-1+/TIM-3+peripheral T cells in gastric cancer patients.PD-1+/TIM-3+cells represent the predominant fraction of TILs. PD-1blockadeenhanced cytokine production and the cytotoxicity of TILs and exhibited a synergisticeffect with TIM-3blockade. Collectively, our results suggest that the use of anti-PD-1blockade in combination with anti-TIM-3blockade could restore the cytotoxic activityof TILs in patients with gastric cancer.