Chemotherapy induces immune checkpoint VISTA expression in tumor cells via HIF-2alpha

• Published in: Biochemical pharmacology Vol. 210; p. 115492
• Main Authors: Li, Na, Yang, Shanru, Ren, Yan, Tai, Risheng, Liu, Hua, Wang, Yixuan, Li, Jianing, Wang, Fuyan, Xing, Jingjun, Zhang, Yanru, Zhu, Xiaoxia, Xu, Suling, Hou, Xin, Wang, Geng
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.04.2023
• Subjects: Adaptive Immunity; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Chemotherapy; HIF-2α; Humans; Immune evasion; Melanoma; Neoplasm Recurrence, Local; VISTA; Chemotherapy; VISTA; HIF-2α; DCs; Melanoma; Immune evasion; TILs; TME; RT-qPCR; HIFs
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2023.115492

[Display omitted] •Chemotherapy promotes the expression of VISTA in tumor cells.•HIF-2α mediates chemotherapy-induced VISTA expression.•VISTA overexpression in melanoma cells promotes immune evasion.•VISTA blockade enhances the therapeutic effect of carboplatin. Tumor cells can evade the innate and adaptive immune systems, which play important roles in tumor recurrence and metastasis. Malignant tumors that recur after chemotherapy are more aggressiveciscis, suggesting an increased ability of the surviving tumor cells to evade innate and adaptive immunity. Therefore, in order to reduce patient mortality, it is important to discover the mechanisms by which tumor cells develop resistance to chemotherapeutics. In the present study we focused on the tumor cells that survived chemotherapy. We found that chemotherapy could promote the expression of VISTA in tumor cells, and that this change was mediated by HIF-2α. In addition, VISTA overexpression on melanoma cells promoted immune evasion, and the application of the VISTA-blocking antibody 13F3 enhanced the therapeutic effect of carboplatin. These results offer an insight into the immune evasion of chemotherapy-resistant tumors, and provide a theoretical basis for the combined application of chemotherapy drugs and VISTA inhibitors to treat tumors.