新型免疫检查点抑制剂T细胞免疫球蛋白和免疫受体酪氨酸抑制性基序结构域在抗肿瘤免疫治疗中的研究进展  

Research progress of a new immune checkpoint inhibitor T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain in anti-tumor immunotherapy

作　　者：孙一彬 姚晓文 于晓辉 张久聪 SUN Yi-bin;YAO Xiao-wen;YU Xiao-hui;ZHANG Jiu-cong(The Physical Examination Center of People's Hospital,Wenjiang District,Chengdu,Sichuan 611130,China;The First Clinical Medical College of Gansu University of Chinese Medicine,Lanzhou,Gansu 730030,China;Department of Gastroenterology,The 940th Hospital of Joint Logistic Support Force of PLA,Lanzhou,Gansu 730050,China)

机构地区：[1]成都市温江区人民医院健康管理体检中心,四川成都611130 [2]甘肃中医药大学第一临床医学院,甘肃兰州730030 [3]中国人民解放军联勤保障部队第九四〇医院消化内科,甘肃兰州730050

出　　处：《中国热带医学》2023年第2期191-195,共5页China Tropical Medicine

基　　金：国家自然科学基金青年科学基金项目(No.81500454);中国博士后科学基金项目(No.2019M653974);第九四〇医院院内拔尖科研项目(No.2021yxky002);军队医药卫生科研项目(No.CLZ15JA02)。

摘　　要：T细胞免疫球蛋白和免疫受体酪氨酸抑制性基序结构域[T-cell immunoglobulin and immunoreceptor tyrosinebased inhibitory motif(ITIM)domain,TIGIT]是新型T细胞或NK细胞抑制性受体,可通过与肿瘤细胞、被感染细胞表面的多种配体相结合,激活免疫细胞内部负性刺激信号,从而抑制细胞过度活化和促炎性细胞因子的过度分泌,在肿瘤、病毒感染以及多种自身免疫性疾病的免疫发病机制中发挥重要的调节功能。最近,TIGIT在癌症免疫治疗中受到了广泛关注,研究显示,TIGIT在癌症患者T细胞和NK细胞中表达升高,且与疾病进展和不良临床预后相关,研究者尝试通过阻断TIGIT与其配体的结合来增强T细胞或NK细胞的活性以进行治疗干预。目前已经有很多关于在不同小鼠肿瘤模型中使用抗TIGIT单抗治疗导致瘤体消退的相关报道,TIGIT有望成为下一代癌症免疫治疗的靶点,现在一些临床试验正在评估抗TIGIT单克隆抗体对不同类型癌症患者的疗效。最近,抗TIGIT单抗(tiragolumab)在与抗程序性死亡受体-配体1(programmed cell death ligand 1, PD-L1)药物联合治疗非小细胞肺癌时表现出显著临床疗效,然而TIGIT阻断治疗的具体作用机制还有待阐明。The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain(TIGIT) is an inhibitory receptor mainly expressed on active T-cells, or natural killer cells(NK cells) that activate negative stimulus signals in immune cells by combining with multiple ligands on the surface of target cells including tumor cells and infected cells.TIGIT plays an important regulatory role in the immune pathogenesis of tumors, viral infections and various autoimmune diseases by inhibiting the over activation of cells and the over secretion of proinflammatory cytokines. Recent researches show that TIGIT is highly expressed in T cells and NK cells of cancer patients, and is related to disease progression and poor clinical prognosis. Researchers try to enhance the activity of T cells or NK cells by blocking the binding of TIGIT and its ligand for therapeutic intervention. At present, there have been many reports about the use of anti-TIGIT monoclonal antibody treatment in different mouse tumor models leading to tumor regression, TIGIT has received extensive attention in cancer immunotherapy as a promising target for next generation cancer immunotherapy. Several clinical trials are currently evaluating the efficacy of anti-TIGIT monoclonal antibodies(mAbs) in patients with several cancers. The most advanced candidate, tiragolumab, has exhibited remarkable efficacy in programmed cell death ligand 1(PD-L1)-positive non-small cell lung carcinoma(NSCLC)patients in phase Ⅱ clinical trials, in combination with PD-L1 blockade. However, the specific mechanism of TIGIT blockade remains to be fully elucidated.

关 键 词：T细胞免疫球蛋白和免疫受体酪氨酸抑制性基序结构域 抗肿瘤免疫 抑制性受体 免疫检查点阻断 

分 类 号：R730[医药卫生—肿瘤]