Immune-Mediated Antitumor Effect By VEGFR2 Selective Inhibitor For Gastric Cancer
| Autor: | Ju Yang, Naiqing Ding, Juan Cai, Qin Wang, Qiuping Xu, Baorui Liu, Fangjun Chen, Shiyao Du, Jing Yan, Fanyan Meng, Shujuan Zhou, Jie Shao |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Chemistry Growth factor medicine.medical_treatment Cancer medicine.disease In vitro 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Cytokine Immune system Oncology In vivo 030220 oncology & carcinogenesis medicine Cancer research Pharmacology (medical) Cytotoxicity CD8 |
| Zdroj: | OncoTargets and Therapy. 12:9757-9765 |
| ISSN: | 1178-6930 |
| Popis: | 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-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. |
| Databáze: | OpenAIRE |
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