Zhang Peng, Liu Xinyuan, Gu Zhuoyu, Jiang Zhongxing, Zhao Song, Song Yongping, Yu Jifeng
Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Henan Medical Key Laboratory of Thoracic Oncology, Zhengzhou, 450052, Henan, China.
Biomark Res. 2024 Jan 16;12(1):7. doi: 10.1186/s40364-023-00543-z.
As a newly identified checkpoint, T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is highly expressed on CD4 T cells, CD8 T cells, natural killer (NK) cells, regulatory T cells (Tregs), and tumor-infiltrating lymphocytes (TILs). TIGIT has been associated with NK cell exhaustion in vivo and in individuals with various cancers. It not only modulates NK cell survival but also mediates T cell exhaustion. As the primary ligand of TIGIT in humans, CD155 may be the main target for immunotherapy due to its interaction with TIGIT. It has been found that the anti-programmed cell death protein 1 (PD-1) treatment response in cancer immunotherapy is correlated with CD155 but not TIGIT. Anti-TIGIT alone and in combination with anti-PD-1 agents have been tested for cancer immunotherapy. Although two clinical studies on advanced lung cancer had positive results, the TIGIT-targeted antibody, tiragolumab, recently failed in two new trials. In this review, we highlight the current developments on TIGIT for cancer immunotherapy and discuss the characteristics and functions of TIGIT.
作为一种新发现的免疫检查点，具有免疫球蛋白和基于酪氨酸的抑制性基序（ITIM）结构域的T细胞免疫受体（TIGIT）在CD4 T细胞、CD8 T细胞、自然杀伤（NK）细胞、调节性T细胞（Tregs）和肿瘤浸润淋巴细胞（TILs）上高表达。TIGIT在体内以及患有各种癌症的个体中均与NK细胞耗竭有关。它不仅调节NK细胞的存活，还介导T细胞耗竭。作为人类TIGIT的主要配体，CD155因其与TIGIT的相互作用可能成为免疫治疗的主要靶点。研究发现，癌症免疫治疗中抗程序性细胞死亡蛋白1（PD-1）的治疗反应与CD155相关，而与TIGIT无关。单独使用抗TIGIT以及与抗PD-1药物联合使用已在癌症免疫治疗中进行了测试。尽管两项针对晚期肺癌的临床研究取得了阳性结果，但TIGIT靶向抗体替雷戈单抗最近在两项新试验中失败。在本综述中，我们重点介绍了TIGIT在癌症免疫治疗方面的最新进展，并讨论了TIGIT的特征和功能。
