免疫检查点
免疫系统
T细胞
效应器
癌症免疫疗法
免疫疗法
CD8型
细胞毒性T细胞
生物
抗体
细胞生物学
免疫学
癌症研究
体外
生物化学
作者
Hieu Minh Ta,Dia Roy,Keman Zhang,Tyler J. Alban,Ivan Jurić,Juan Dong,Prerana Bangalore Parthasarathy,Sachin Patnaik,Elizabeth Delaney,Cassandra Gilmour,Amin Zakeri,Nidhi Shukla,Amit Rupani,Yee Peng Phoon,Caini Liu,Stefanie Avril,Brian Gastman,Timothy A. Chan,Li Lily Wang
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2024-05-17
卷期号:9 (95)
被引量:5
标识
DOI:10.1126/sciimmunol.adi7418
摘要
Immune checkpoint blockade is a promising approach to activate antitumor immunity and improve the survival of patients with cancer. V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint target; however, the downstream signaling mechanisms are elusive. Here, we identify leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) as a VISTA binding partner, which acts as an inhibitory receptor by engaging VISTA and suppressing T cell receptor signaling pathways. Mice with T cell–specific LRIG1 deletion developed superior antitumor responses because of expansion of tumor-specific cytotoxic T lymphocytes (CTLs) with increased effector function and survival. Sustained tumor control was associated with a reduction of quiescent CTLs (TCF1 + CD62L hi PD-1 low ) and a reciprocal increase in progenitor and memory-like CTLs (TCF1 + PD-1 + ). In patients with melanoma, elevated LRIG1 expression on tumor-infiltrating CD8 + CTLs correlated with resistance to immunotherapies. These results delineate the role of LRIG1 as an inhibitory immune checkpoint receptor and propose a rationale for targeting the VISTA/LRIG1 axis for cancer immunotherapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI