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VISTA: A Mediator of Quiescence and a Promising Target in Cancer Immunotherapy

机译:Vista:静态的介质和癌症免疫疗法的有希望的靶标

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V-domain Ig suppressor of T cell activation (VISTA) is a B7 family member that maintains T cell and myeloid quiescence and is a promising target for combination cancer immunotherapy. During inflammatory challenges, VISTA activity reprograms macrophages towards reduced production of proinflammatory cytokines and increased production of interleukin (IL)-10 and other anti-inflammatory mediators. The interaction of VISTA with its ligands is regulated by pH, and the acidic pH -6.0 in the tumor microenvironment (TME) facilitates VISTA binding to P-selectin glycoprotein ligand 1 (PSGL-1). Targeting intratumoral pH might be a way to reduce the immunoinhibitory activity of the VISTA pathway and enhance antitumor immune responses. We review differences among VISTA therapeutics under development as candidate immunotherapies, focusing on VISTA binding partners and the unique structural features of this interaction.
机译:V域Ig T细胞激活抑制因子(VISTA)是一个B7家族成员,可维持T细胞和髓系静止,是联合癌症免疫治疗的一个有希望的靶点。在炎症挑战期间,VISTA活动重新编程巨噬细胞,使其减少促炎细胞因子的产生,增加白细胞介素(IL)-10和其他抗炎介质的产生。VISTA与其配体的相互作用受pH调节,肿瘤微环境(TME)中的酸性pH-6.0促进VISTA与P-选择素糖蛋白配体1(PSGL-1)的结合。靶向肿瘤内pH可能是一种降低VISTA途径免疫抑制活性并增强抗肿瘤免疫反应的方法。我们回顾了作为候选免疫疗法正在开发的VISTA疗法之间的差异,重点是VISTA结合伙伴和这种相互作用的独特结构特征。

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