Program in Immunology, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Trends Immunol. 2021 Mar;42(3):209-227. doi: 10.1016/j.it.2020.12.008. Epub 2021 Jan 23.
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.
V 结构域免疫球蛋白抑制 T 细胞活化因子（VISTA）是 B7 家族成员，可维持 T 细胞和髓系细胞静止，是联合癌症免疫疗法的有前途的靶点。在炎症性挑战期间，VISTA 活性将巨噬细胞重新编程为减少促炎细胞因子的产生和增加白细胞介素（IL）-10 和其他抗炎介质的产生。VISTA 与其配体的相互作用受 pH 值调节，肿瘤微环境（TME）中的酸性 pH 值~6.0 有利于 VISTA 与 P 选择素糖蛋白配体 1（PSGL-1）结合。靶向肿瘤内 pH 值可能是减少 VISTA 途径免疫抑制活性和增强抗肿瘤免疫反应的一种方法。我们综述了作为候选免疫疗法正在开发的 VISTA 治疗药物之间的差异，重点关注 VISTA 结合伙伴和这种相互作用的独特结构特征。
