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


ABSTRACT: Background: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-? 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.

SUBMITTER: Yang J 

PROVIDER: S-EPMC6863181 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Yang Ju J   Yan Jing J   Shao Jie J   Xu Qiuping Q   Meng Fanyan F   Chen Fangjun F   Ding Naiqing N   Du Shiyao S   Zhou Shujuan S   Cai Juan J   Wang Qin Q   Liu Baorui B  

OncoTargets and therapy 20191115


<h4>Background</h4>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.<h4>Materials and methods</h4>In this study, we investigated the effects of YN968D1 on the function of T cells in vitro by testing the cytotoxicity and cytokine prod  ...[more]

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