Immune-Mediated Antitumor Effect By VEGFR2 Selective Inhibitor For Gastric Cancer

Abstract

Ju Yang, Jing Yan, Jie Shao, Qiuping Xu, Fanyan Meng, Fangjun Chen, Naiqing Ding, Shiyao Du, Shujuan Zhou, Juan Cai, Qin Wang, Baorui Liu The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing 210008, People’s Republic of ChinaCorrespondence: Baorui LiuThe Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing 210008, People’s Republic of ChinaEmail [email protected]: It was previously reported that targeting vascular epithelial growth factor (VEGF)/VEGFR could modulate the antitumor immunity. VEGFR2 inhibitor YN968D1 is a highly selective VEGFR2 inhibitor and was approved for the treatment of late-stage gastric cancer in 2014, but its role in antitumor immunity remains unknown.Materials and methods: In this study, we investigated the effects of YN968D1 on the function of T cells in vitro by testing the cytotoxicity and cytokine production. Next, we constructed peritoneal dissemination and subcutaneous gastric cancer mouse model to assess the cytotoxicity of YN968D1-treated T cells in vivo, respectively.Results: We found that the use of YN968D1 in CD8+ T cells could reduce the expression levels of inhibitory checkpoints, such as Lag-3, PD-1, and Tim3, escalate the production of IFN-γ and IL-2 and promote the cytotoxicity of T cells dramatically in vitro. The transfer of YN968D1-treated T cells achieved better tumor control compared to DMSO-treated T cells or control in both peritoneal dissemination and subcutaneous gastric cancer mouse models.Conclusion: Our results indicate that YN968D1 can enhance the T cell-mediated antitumor immunity.Keywords: YN968D1, gastric cancer, T cells, cytotoxicity, anti-tumor immunity  

Keywords

• yn968d1
• gastric cancer
• t cells
• cytotoxicity
• anti-tumor immunity