Wen Yuanjia, Xia Yu, Yang Xiangping, Li Huayi, Gao Qinglei
Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
The Second Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, Guangzhou, China.
Trends Immunol. 2025 Feb;46(2):153-165. doi: 10.1016/j.it.2025.01.001. Epub 2025 Jan 30.
Tumor-infiltrating regulatory T (TI-Treg) cells constitute key components within the tumor microenvironment (TME) to suppress antitumor immunity and facilitate tumor progression. Although multiple therapies have been developed to eliminate TI-Treg cells, most of them exhibit only modest efficacy and harbor risks of inducing immune-related adverse events (irAEs). Recent studies demonstrate that CC chemokine receptor (CCR)8 is highly and specifically expressed on effector TI-Treg cells in mice and humans, highlighting CCR8 as a promising target for selective TI-Treg cell depletion in the treatment of various cancers. Here, we concentrate on the latest understanding of CCR8 regarding its expression, functions, and regulation, and summarize the current landscape of CCR8-targeted therapies. With favorable efficacy and safety, the latter represent an important class of next-generation putative cancer immunotherapies.
肿瘤浸润调节性T(TI-Treg)细胞是肿瘤微环境(TME)中抑制抗肿瘤免疫并促进肿瘤进展的关键组成部分。尽管已经开发了多种疗法来消除TI-Treg细胞,但大多数疗法仅显示出适度的疗效,并且存在引发免疫相关不良事件(irAE)的风险。最近的研究表明,CC趋化因子受体(CCR)8在小鼠和人类的效应TI-Treg细胞上高度特异性表达,这突出了CCR8作为在各种癌症治疗中选择性耗尽TI-Treg细胞的一个有前景的靶点。在此,我们专注于对CCR8在其表达、功能和调节方面的最新认识,并总结CCR8靶向疗法的当前情况。后者具有良好的疗效和安全性,代表了一类重要的下一代潜在癌症免疫疗法。