Department of Cancer Immunology, Genentech, South San Francisco, CA, USA.
Department of Cancer Immunology, Genentech, South San Francisco, CA, USA.
Trends Immunol. 2017 Jan;38(1):20-28. doi: 10.1016/j.it.2016.10.002. Epub 2016 Oct 25.
Immunotherapies that harness the activity of the immune system against tumors are proving to be an effective therapeutic approach in multiple malignancies. Indeed, through accumulation of genetic mutations, many tumors express antigens that can potentially elicit specific tumor immunity. However, tumors can also suppress these responses by activating negative regulatory pathways and checkpoints such as PD-1/PD-L1 and CTLA-4. Blocking these checkpoints on T cells has provided dramatic clinical benefit, but only a subset of patients exhibit clear and durable responses, suggesting that other mechanisms must be limiting the immune response. We discuss here the role of TIGIT, an inhibitory receptor expressed by lymphocytes, in limiting antitumor responses and we review its mechanisms of action during the cancer immunity cycle.
免疫疗法利用免疫系统对抗肿瘤的活性,已被证明在多种恶性肿瘤中是一种有效的治疗方法。事实上,许多肿瘤通过积累基因突变表达抗原,这些抗原有可能引发特异性肿瘤免疫。然而,肿瘤也可以通过激活负调节途径和检查点(如 PD-1/PD-L1 和 CTLA-4)来抑制这些反应。阻断 T 细胞上的这些检查点提供了显著的临床获益,但只有一部分患者表现出明确和持久的反应,这表明其他机制一定限制了免疫反应。我们在这里讨论了表达在淋巴细胞上的抑制性受体 TIGIT 在限制抗肿瘤反应中的作用,并回顾了其在癌症免疫周期中的作用机制。