靶向代谢物感应G蛋白偶联受体的肿瘤免疫治疗药物临床研究进展

Clinical Research Progress of Drugs Targeting Metabolite-Sensing G Protein-Coupled Receptors for Tumor Immunotherapy

摘要

G蛋白偶联受体（G protein-coupled receptor，GPCR）是人体基因组中最大的跨膜信号转导受体家族，在肿瘤等重大疾病的发生发展进程中发挥关键调控作用。近年来研究表明，代谢物感应GPCR可特异性识别并感应多种肿瘤相关代谢产物，激活免疫抑制信号，进而诱导肿瘤免疫逃逸及耐药，现已成为肿瘤免疫治疗领域的前沿靶点。阐述以前列腺素受体和腺苷受体为代表的代谢物感应GPCR驱动肿瘤免疫逃逸的作用机制。同时，重点梳理靶向这两类受体的药物研发成果与最新临床研究进展，深入分析这两类靶向药物在临床转化过程中面临的机遇与挑战，以期为新一代肿瘤免疫治疗药物的研发提供新视角与新思路。

Abstract

G protein-coupled receptors (GPCRs), the largest family of transmembrane signal transducers in human genome, play pivotal regulatory roles in the initiation and progression of major diseases including cancer. Recent studies have shown that metabolite-sensing GPCRs can specifically recognize and respond to various tumor-associated metabolites, thereby activating immunosuppressive signals, and further inducing tumor immune escape and drug resistance, rendering them frontier targets in the field of tumor immunotherapy. This review elucidates the mechanisms by which metabolite-sensing GPCRs represented by prostaglandin and adenosine receptors drive tumor immune escape. Meanwhile, it summarizes the key achievements in drug development and the latest clinical research progress targeting these two types of receptors, and conducts in-depth analysis of the opportunities and challenges faced by such targeting drugs in the process of clinical translation, so as to provide new perspectives and insights for the development of next-generation tumor immunotherapeutic agents.

关键词

G蛋白偶联受体 / 代谢产物 / 免疫治疗 / 免疫反应

Key words

G protein-coupled receptor / metabolite / immunotherapy / immune response

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基金资助

国家自然科学基金资助项目(82574452)