Identification of Co-inhibitory Receptors PD-1 and TIM-3 on T Cells from Gastric Cancer PatientsYunhui Zong1,3,9,#, Songbing He2,#, Fuliang Chu4,5, Yu Jing6, Sally A Hunsucker7, Tina Yang8, Fengtao You3,4,5, Sisi Ye3,4,5, Yafen Li1,3,9, Jinle Tang1,9, Huimin Meng1,9, Gangli An1,9, Xingding Zhang3,4,5, Bozhen Zhang3,4,5, Lin Yang1,3,4,5,9*
- *Corresponding Author:
- Lin Yang
The Cyrus Tang Hematology Center
Soochow University, 199 Ren’ai Road
SIP, Suzhou, Jiangsu, PR China, 215123
Tel: +86 (512) 6588 0877
Fax: +86 (512) 6588 1544
E-mail: [email protected]
Received date: September 21, 2015; Accepted date: November 18, 2015; Published date: November 23, 2015
Citation: Zong Y, He S, Chu F, Jing Y, Hunsucker SA, et al. (2015) Identification of Co-inhibitory Receptors PD-1 and TIM-3 on T Cells from Gastric Cancer Patients. Immunother Open Acc 1:105. doi: 10.4172/2471-9552.1000105
Copyright: © 2015 Zong Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The critical role of tumor antigen-specific immune responses to restrain tumor growth in patients with gastric cancer furthers the need to dissect the co-inhibitory pathways involved in tumor 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. 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. Moreover, the expression of PD-1 was associated with the age, tumor size and lymph node metastasis of patients. Collectively, our results suggest that the use of anti-PD-1 blockade in combination with anti-TIM-3 blockade could restore the function of TILs in patients with gastric cancer.