Cancer Immunology, Genentech Inc, South San Francisco, California, USA.
Cancer Immunology, Genentech Inc, South San Francisco, California, USA
J Immunother Cancer. 2022 Apr;10(4). doi: 10.1136/jitc-2022-004711.
Recent advances in understanding the roles of immune checkpoints in allowing tumors to circumvent the immune system have led to successful therapeutic strategies that have fundamentally changed oncology practice. Thus far, immunotherapies against only two checkpoint targets have been approved, CTLA-4 and PD-L1/PD-1. Antibody blockade of these targets enhances the function of antitumor T cells at least in part by relieving inhibition of the T cell costimulatory receptor CD28. These successes have stimulated considerable interest in identifying other pathways that may bte targeted alone or together with existing immunotherapies. One such immune checkpoint axis is comprised of members of the PVR/nectin family that includes the inhibitory receptor T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains (TIGIT). Interestingly, TIGIT acts to regulate the activity of a second costimulatory receptor CD226 that works in parallel to CD28. There are currently over two dozen TIGIT-directed blocking antibodies in various phases of clinical development, testament to the promise of modulating this pathway to enhance antitumor immune responses. In this review, we discuss the role of TIGIT as a checkpoint inhibitor, its interplay with the activating counter-receptor CD226, and its status as the next advance in cancer immunotherapy.
近年来，人们对免疫检查点在肿瘤逃避免疫系统方面的作用的认识不断深入，这使得成功的治疗策略得以出现，并从根本上改变了肿瘤学的实践。到目前为止，仅有两种检查点靶点的免疫疗法获得批准，即 CTLA-4 和 PD-L1/PD-1。这些靶点的抗体阻断至少部分通过解除 T 细胞共刺激受体 CD28 的抑制作用来增强抗肿瘤 T 细胞的功能。这些成功极大地激发了人们寻找其他可能单独或与现有免疫疗法联合靶向的途径的兴趣。其中一个免疫检查点轴由 PVR/nectin 家族成员组成，包括抑制性受体 T 细胞免疫受体 Ig 和免疫受体酪氨酸抑制基序（TIGIT）。有趣的是，TIGIT 作用于调节与 CD28 平行起作用的第二个共刺激受体 CD226 的活性。目前，有二十多种针对 TIGIT 的阻断抗体处于不同的临床开发阶段，这证明了调节该途径以增强抗肿瘤免疫反应的前景。在这篇综述中，我们讨论了 TIGIT 作为检查点抑制剂的作用、它与激活性拮抗受体 CD226 的相互作用，以及它作为癌症免疫治疗下一个进展的地位。
