Abstract 4094: Identification of co-inhibitory receptor expression on T cells from gastric cancer patients

Abstract The critical role of tumour antigen-specific immune responses to restrain tumour growth in patients with gastric cancer furthers the need to dissect the co-inhibitory pathways involved in tumour infiltrating lymphocyte (TIL) exhaustion/dysfunction. It was previously reported that PD-1 expression was significantly increased on CD4+ and CD8+ T cells from patients with gastric cancer and in gastric cancer tissues, compared to normal donors. In this study, we observed up-regulation of TIM-3 and PD-1 expression on peripheral T cells and up-regulation of CTLA-4, TIGIT, TIM-3 and PD-1 expression on TILs from gastric cancer patients; however TIGIT was down-regulated on CD8+ TILs and TIM-3 up-regulation on CD8+ TILs was not statistically significant. Furthermore, the percentages of PD-1+/TIM-3+ and PD-1+/TIM-3- peripheral T cells was significantly higher in gastric cancer patients than normal donors, and the percentage of PD-1+/TIM-3+ TILs was significantly higher than the 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-1 blockade enhanced cytokine production and the cytotoxicity of TILs and exhibited a synergistic effect with TIM-3 blockade. Collectively, our results suggest that the use of anti-PD-1 blockade in combination with anti-TIM-3 blockade could restore the cytotoxic activity of TILs in patients with gastric cancer. Citation Format: Yunhui Zong, Fuliang Chu, Songbing He, Yu Jing, Sally A Hunsucker, Tina Yang, Ming Zhang, Sisi Ye, Yafen Li, Bin Liu, Jinle Tang, Huimin Meng, Gangli An, Lin Yang. Identification of co-inhibitory receptor expression on T cells from gastric cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4094. doi:10.1158/1538-7445.AM2014-4094