肿瘤特异性 CD8 细胞毒性 T 细胞的分化、存活和效应功能是抗肿瘤免疫的核心。由于缺乏适当的共刺激和丰富的免疫抑制机制，肿瘤特异性T细胞表现出缺乏持久性、疲惫和功能失调的表型。多种共抑制受体，例如 PD-1、CTLA-4、VISTA、TIGIT、TIM-3 和 LAG-3，会导致 CTL 功能失调和抗肿瘤免疫失败。这些共抑制受体统称为免疫检查点受体（ICR）。针对这些 ICR 的免疫检查点抑制剂 (ICIs) 已成为癌症免疫治疗的基石，因为它们为范围不断扩大的以前无法治疗的癌症建立了新的临床范例。鉴于各种 ICR 介导的非冗余但趋同的分子途径，正在测试组合免疫疗法，以期为患者带来协同效益。在这篇综述中，我们总结了几种新兴 ICR 的机制，包括 VISTA、TIGIT、TIM-3 和 LAG-3，以及支持改善现有 ICI 疗法的组合策略的临床前和临床数据。版权所有 © 2023 Roy、Gilmour、Patnaik和王。

The differentiation, survival, and effector function of tumor-specific CD8+ cytotoxic T cells lie at the center of antitumor immunity. Due to the lack of proper costimulation and the abundant immunosuppressive mechanisms, tumor-specific T cells show a lack of persistence and exhausted and dysfunctional phenotypes. Multiple coinhibitory receptors, such as PD-1, CTLA-4, VISTA, TIGIT, TIM-3, and LAG-3, contribute to dysfunctional CTLs and failed antitumor immunity. These coinhibitory receptors are collectively called immune checkpoint receptors (ICRs). Immune checkpoint inhibitors (ICIs) targeting these ICRs have become the cornerstone for cancer immunotherapy as they have established new clinical paradigms for an expanding range of previously untreatable cancers. Given the nonredundant yet convergent molecular pathways mediated by various ICRs, combinatorial immunotherapies are being tested to bring synergistic benefits to patients. In this review, we summarize the mechanisms of several emerging ICRs, including VISTA, TIGIT, TIM-3, and LAG-3, and the preclinical and clinical data supporting combinatorial strategies to improve existing ICI therapies.Copyright © 2023 Roy, Gilmour, Patnaik and Wang.