Huang Chenshen, Zhu Fengshuo, Zhang Hao, Wang Ning, Huang Qi
Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
iScience. 2023 Aug 19;26(9):107693. doi: 10.1016/j.isci.2023.107693. eCollection 2023 Sep 15.
G protein-coupled receptors (GPCRs) are the largest family of membrane proteins and play a critical role as pharmacological targets. An improved understanding of GPCRs' involvement in tumor microenvironment may provide new perspectives for cancer therapy. This study used machine learning to classify head and neck squamous cell carcinoma (HNSCC) patients into two GPCR-based subtypes. Notably, these subtypes showed significant differences in prognosis, gene expression, and immune microenvironment, particularly CD8 T cell infiltration. S1PR4 emerged as a key regulator distinguishing the subtypes, positively correlated with CD8 T cell proportion and cytotoxicity in HNSCC. It was predominantly expressed in CX3CR1CD8 T cells among T cells. Upregulation of S1PR4 enhanced T cell function during CAR-T cell therapy, suggesting its potential in cancer immunotherapy. These findings highlight S1PR4 as an immune modulator for favorable prognosis in HNSCC, and offer a potential GPCR-targeted therapeutic option for HNSCC treatment.
G蛋白偶联受体（GPCRs）是最大的膜蛋白家族，作为药理学靶点发挥着关键作用。对GPCRs参与肿瘤微环境的深入了解可能为癌症治疗提供新的视角。本研究使用机器学习将头颈部鳞状细胞癌（HNSCC）患者分为两种基于GPCR的亚型。值得注意的是，这些亚型在预后、基因表达和免疫微环境方面存在显著差异，尤其是CD8 T细胞浸润。S1PR4成为区分这些亚型的关键调节因子，与HNSCC中CD8 T细胞比例和细胞毒性呈正相关。它在T细胞中的CX3CR1⁺CD8 T细胞中主要表达。S1PR4的上调在CAR-T细胞治疗期间增强了T细胞功能，表明其在癌症免疫治疗中的潜力。这些发现突出了S1PR4作为HNSCC预后良好的免疫调节剂，并为HNSCC治疗提供了一种潜在的GPCR靶向治疗选择。
