免疫检查点通过代谢途径介导肿瘤免疫调控  

Immune Checkpoints Mediate Tumor Immune Regulation through Metabolic Pathways

作　　者：杜伟光 唐希阳 周玉龙 李梦超 金泽 窦家琪 赵晋波 Weiguang DU;Xiyang TANG;Yulong ZHOU;Mengchao LI;Ze JIN;Jiaqi DOU;Jinbo ZHAO(Graduate School of Xi'an Medical University,Xi'an 710021,China;Department of Thoracic Surgery,Tangdu Hospital,Air Force Medical University,Xi'an 710038,China;College of Basic Medicine,Air Force Medical University,Xi'an 710032,China)

机构地区：[1]西安医学院研究生部,西安710021 [2]空军军医大学唐都医院胸腔外科,西安710038 [3]空军军医大学基础医学院,西安710032

出　　处：《中国肺癌杂志》2025年第3期213-220,共8页Chinese Journal of Lung Cancer

基　　金：陕西省杰出青年科学基金项目(No.S2024-JC-JQ-0387)资助。

摘　　要：免疫检查点包括一系列在免疫细胞的增殖、活化以及免疫调控反应中发挥关键作用的受体-配体对。尽管目前免疫检查点抑制剂(immune checkpoint inhibitors,ICIs),如程序性死亡受体-1(programmed death protein 1,PD-1)、细胞毒性T淋巴细胞相关蛋白4(cytotoxic T-lymphocyte-associated protein 4,CTLA-4)在临床中已取得较好的疗效,但部分患者仍然存在治疗无效和免疫耐药的问题。已有大量证据表明,免疫检查点蛋白在免疫调节过程中与细胞代谢相关。一方面免疫检查点连接改变肿瘤细胞代谢重编程竞争免疫细胞所需的营养,另一方面免疫检查点通过调节免疫细胞代谢通路,如磷脂酰肌醇3激酶/蛋白激酶B/雷帕霉素靶蛋白(phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin,PI3K/AKT/mTOR)影响免疫细胞的激活。基于对既往文献的回顾,本文对PD-1、CTLA-4、T细胞免疫球蛋白和ITIM结构域蛋白(T cell immunoreceptor with Ig and ITIM domains,TIGIT)、T细胞免疫球蛋白和黏蛋白结构域蛋白3(T cell immunoglobulin and mucin domain-containing protein 3,TIM-3)、分化簇47(cluster of differentiation 47,CD47)、吲哚胺2,3-双加氧酶1(indoleamine 2,3-dioxygenase 1,IDO1)如何调控细胞代谢重编程的机制进行综述,并且对靶向免疫检查点配体-受体对的a双重调控o及抑制代谢途径是否有效解决肿瘤免疫耐药的问题进行展望。Immune checkpoints include a series of receptor-ligand pairs that play a key role in the proliferation,activation,and immune regulatory responses of immune cells.Although immune checkpoint inhibitors(ICIs),such as pro-grammed death protein 1(PD-1)and cytotoxic T-lymphocyte-associated protein 4(CTLA-4)have achieved good therapeu-tic effects in clinical practice,some patients still experience ineffective treatment and immune resistance.A large amount of evidence has shown that immune checkpoint proteins are related to cell metabolism during immune regulation.On the one hand,immune checkpoints connect to alter the metabolic reprogramming of tumor cells to compete for nutrients required by immune cells.On the other hand,immune checkpoints regulate the metabolic pathways of immune cells,such as phosphati-dylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)to affect the activation of immune cells.Based on a review of the literature,this article reviews the mechanisms by which PD-1,CTLA-4,T cell immunoreceptor with Ig and ITIM domains(TIGIT),T cell immunoglobulin and mucin domain-containing protein 3(TIM-3),cluster of dif-ferentiation 47(CD47),and indoleamine 2,3-dioxygenase 1(IDO1)regulate cell metabolic reprogramming,and looks forward to whether targeting the ligand-receptor pairs of immune checkpoints in a"dual regulation"manner and inhibiting metabolic pathways can effectively solve the problem of tumor immune resistance.

关 键 词：免疫检查点 肿瘤微环境 免疫代谢 肿瘤免疫 

分 类 号：R73[医药卫生—肿瘤]