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通过机器学习鉴定 S1PR4 作为 HNSCC 良好预后的免疫调节因子

英文原题:Identification of S1PR4 as an immune modulator for favorable prognosis in HNSCC through machine learning.

查看英文原题

Identification of S1PR4 as an immune modulator for favorable prognosis in HNSCC through machine learning.

PubMed 2023/08/19(内容时间) iScience Q1 · IF 4.5(JCR 2025)

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中文摘要

G 蛋白偶联受体(GPCR)是最大的膜蛋白家族,是重要的药理学靶点。更深入理解 GPCR 参与肿瘤微环境的方式,可能为癌症治疗提供新思路。本研究采用机器学习,根据 GPCR 将头颈部鳞状细胞癌(HNSCC)患者分为两种亚型。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 是区分两种亚型的关键调节因子,在 HNSCC 中与 CD8⁺ T 细胞比例和细胞毒性呈正相关。该基因主要在 T 细胞中的 CX3CR1⁺CD8⁺ T 细胞中表达。上调 S1PR4 可增强 CAR-T 细胞治疗期间的 T 细胞功能,提示其在癌症免疫治疗中的潜力。这些发现凸显 S1PR4 作为有利预后免疫调节因子的作用,并为 HNSCC 治疗提供了潜在的 GPCR 靶向治疗选择。

展开英文摘要原文

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 CX3CR1 + CD8 + 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.

论文信息

作者
Huang C、Zhu F、Zhang H、Wang N、Huang Q
第一作者单位
Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.China
通讯作者单位
Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.China
期刊
iScience2023 Sep 15
原文标识
PubMed 37680482 · DOI 10.1016/j.isci.2023.107693