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T细胞激活抑制物免疫球蛋白可变区结构域(VISTA)是可抑制T细胞应答的负向免疫检查点分子,主要表达于造血细胞,具有受体和配体的双重功能,在肿瘤微环境和肿瘤浸润淋巴结中表达升高。VISTA可抑制T细胞对肿瘤抗原的应答,抑制T细胞分化为调节性T细胞(Treg),降低白细胞介素2(IL-2)的产生,具有免疫抑制和免疫调节的功能。但是VISTA并不会对B细胞的增殖产生影响。VISTA与转移性黑素瘤、诱导性黑素瘤和年龄相关的炎症表型的发生相关,并且具有与不同于程序性死亡蛋白1及配体1(PD-1/PD-L1)信号通路,联用VISTA/PD-1的单克隆抗体可取得更好的治疗效果。此外,VISTA在小鼠急性移植物抗宿主疾病模型上也表现出显著的调节作用。VISTA在免疫抑制中具有明确的功能,可能是这一生物学行为的核心控制元件,然而其天然配体及其发挥作用的内在机制尚不清楚。提示我们VISTA作为新发现的负向免疫检查点有望成为肿瘤免疫治疗的新靶点。
T cell activation inhibitor Immunoglobulin variable region (VISTA) is a negative immune checkpoint molecule that can inhibit T cell responses, mainly expressed in hematopoietic cells, with the dual functions of receptors and ligands. In the tumor microenvironment And tumor infiltrating lymph nodes in the expression increased. VISTA can suppress the T cell response to tumor antigens, inhibit the differentiation of T cells into regulatory T cells (Tregs), reduce the production of interleukin 2 (IL-2), and have immunosuppressive and immunomodulatory functions. However, VISTA does not affect the proliferation of B cells. VISTA is associated with the development of metastatic melanoma, induced melanoma, and age-related inflammatory phenotypes and has the ability to interact with PD-1 / PD-L1 signaling pathways other than PD-1 / PD- The combination of VISTA / PD-1 monoclonal antibody can achieve better therapeutic effect. In addition, VISTA also showed a significant regulatory role in a mouse model of acute graft versus host disease. VISTA has a clear function in immunosuppression and may be the core control element of this biological behavior. However, its natural ligand and the underlying mechanism of its function are not yet clear. Prompted us VISTA as a newly discovered negative immune checkpoint is expected to become a new target for tumor immunotherapy.