Immunoglobulin superfamily member 11 (IGSF11) has recently emerged as a critical immune checkpoint ligand that interacts with the V-domain immunoglobulin suppressor of T-cell activation (VISTA) receptor to inhibit T-cell activation and promote immune escape. Preclinical studies have demonstrated that targeting the IGSF11-VISTA axis effectively reverses immunosuppression by enhancing T-cell effector functions and increasing the secretion of prostimulatory cytokines such as IFN-γ. This immune modulation shifts the tumor microenvironment from an immune “cold” state, characterized by low immune infiltration and activity, to a more immunoreactive “hot” state that is more susceptible to immune-mediated destruction. Moreover, combining IGSF11 inhibition with established therapies such as anti-PD-1/PD-L1 improves treatment efficacy in various cancer models. In this review, we focus on the immunomodulatory functions of IGSF11, its role in combination immunotherapies, and preclinical evidence supporting its potential as a novel therapeutic target to overcome resistance and improve cancer immunotherapy outcomes.
免疫球蛋白超家族成员11（IGSF11）作为一种关键的免疫检查点配体，其通过与T细胞活化抑制性V结构域免疫球蛋白（VISTA）受体相互作用，抑制T细胞活化并促进免疫逃逸。临床前研究表明，靶向IGSF11-VISTA轴能有效逆转免疫抑制，通过增强T细胞效应功能并促进IFN-γ等共刺激细胞因子的分泌。这种免疫调节作用可将肿瘤微环境从免疫浸润及活性低下的“冷”状态，转变为免疫反应性更强的“热”状态，从而更易受到免疫介导的杀伤。此外，在多种癌症模型中，抑制IGSF11与抗PD-1/PD-L1等现有疗法联用可显著提升治疗效果。本综述聚焦于IGSF11的免疫调节功能、其在联合免疫治疗中的作用，以及支持其作为克服耐药性和改善癌症免疫治疗疗效的新型治疗靶点的临床前证据。
IGSF11-Mediated Immune Modulation: Unlocking a Novel Pathway in Emerging Cancer Immunotherapies
肿瘤(癌症)患者之家