细胞毒性
免疫系统
逃避(道德)
癌症研究
免疫学
生物
体外
遗传学
作者
Hao Chi,Shouyan Deng,Ke Xu,Yibo Zhang,Teng Song,Jianghong Yu,Yiting Wang,J Liu,Yuan Zhang,Jiawei Shi,Yungang Wang,Jie Xu
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2024-12-09
标识
DOI:10.1158/0008-5472.can-24-2223
摘要
T cells within the tumor microenvironment frequently exhibit dysfunctional characteristics that compromise their ability to elicit both innate and therapeutic-induced immune responses. Regulators of immune dysfunction represent therapeutic targets to activate anti-tumor immunity. In this study, we identified semaphorin 3G (SEMA3G) as a key regulator of immune responses in cancer. SEMA3G was widely upregulated in diverse human cancers, and its expression was positively correlated with tumor progression. SEMA3G acted as a ligand that inhibited the activation and functionality of T cells. A comprehensive receptor screening approach demonstrated that SEMA3G exhibited a significantly stronger affinity for neuropilin NRP1 compared to NRP2. Furthermore, SEMA3G primarily impeded T-cell functions via NRP1. Disruption of SEMA3G using CRISPR/Cas9 technology or blockade with a neutralizing antibody effectively restored the cytotoxicity of CD8+ T cells and inhibited the growth of tumors in vivo. This research underscores the role of SEMA3G in T-cell dysfunction within tumors and proposes a targeting SEMA3G as a cancer immunotherapeutic strategy.
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