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靶向肿瘤微环境中的GABA信号传导:对免疫细胞调节和免疫治疗抗性的影响

Targeting GABA signaling in the tumor microenvironment: implications for immune cell regulation and immunotherapy resistance.

作者信息

Zhao Yuanqing, Xu Jin, Yang Ke, Bao Li

机构信息

Department of Laboratory Medicine, Clinical Laboratory Medicine Research Center, West China Hospital, Sichuan University, Sichuan Clinical Research Center for LaboratoryMedicine, Chengdu, Sichuan, China.

Department of Laboratory Medicine, Chengdu Shangjin Nanfu Hospital, Chengdu, Sichuan, China.

出版信息

Front Immunol. 2025 Aug 5;16:1645718. doi: 10.3389/fimmu.2025.1645718. eCollection 2025.


DOI:10.3389/fimmu.2025.1645718
PMID:40837580
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12361211/
Abstract

As an important inhibitory neurotransmitter, γ-aminobutyric acid (GABA) not only plays a key role in the central nervous system, but also has attracted wide attention in the tumor immune microenvironment in recent years. Studies have shown that tumor cells can synthesize GABA and use it to remodel the tumor microenvironment, thereby promoting the occurrence, development and metastasis of tumors. Although previous studies have revealed the important role of GABA in tumor immune escape, there are still many unknown areas of its mechanism, especially the heterogeneous manifestations in different tumor types and tissue environments. This review summarizes the immunomodulatory mechanisms of GABA in tumor-associated macrophages, CD8 T cells and dendritic cells in the tumor immune microenvironment, and discusses its potential role in tumor immune escape and immunotherapy resistance, providing new ideas for the development of immunotherapeutic drugs targeting GABA receptors.

摘要

γ-氨基丁酸(GABA)作为一种重要的抑制性神经递质,不仅在中枢神经系统中发挥关键作用,近年来在肿瘤免疫微环境中也备受关注。研究表明,肿瘤细胞能够合成GABA并利用其重塑肿瘤微环境,从而促进肿瘤的发生、发展和转移。尽管先前的研究揭示了GABA在肿瘤免疫逃逸中的重要作用,但其机制仍存在许多未知领域,尤其是在不同肿瘤类型和组织环境中的异质性表现。本文综述了GABA在肿瘤免疫微环境中对肿瘤相关巨噬细胞、CD8 T细胞和树突状细胞的免疫调节机制,并探讨了其在肿瘤免疫逃逸和免疫治疗耐药中的潜在作用,为开发靶向GABA受体的免疫治疗药物提供新思路。

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本文引用的文献

[1]
Harnessing traditional medicine and biomarker-driven approaches to counteract Trichostatin A-induced esophageal cancer progression.

World J Gastroenterol. 2025-5-28

[2]
Paracrine Orchestration of Tumor Microenvironment Remodeling Induced by GLO1 Potentiates Lymph Node Metastasis in Breast Cancer.

Adv Sci (Weinh). 2025-8

[3]
Precision nanomedicine: navigating the tumor microenvironment for enhanced cancer immunotherapy and targeted drug delivery.

Mol Cancer. 2025-6-3

[4]
Deciphering the role of : Insights from pan-cancer multiomics analyses with emphasis on nasopharyngeal carcinoma.

J Transl Int Med. 2025-5-8

[5]
Different strategies for cancer treatment: Targeting cancer cells or their neighbors?

Chin J Cancer Res. 2025-4-30

[6]
The voltage-gated sodium channel β3 subunit modulates C6 glioma cell motility independently of channel activity.

Biochim Biophys Acta Mol Basis Dis. 2025-8

[7]
Activation of the γ-Aminobutyric Acid Receptor Type B Suppresses the Proliferation of Lung Adenocarcinoma Cells.

Anticancer Res. 2025-4

[8]
GABA regulates metabolic reprogramming to mediate the development of brain metastasis in non-small cell lung cancer.

J Exp Clin Cancer Res. 2025-2-19

[9]
Cancer-associated fibroblast-derived extracellular vesicles: regulators and therapeutic targets in the tumor microenvironment.

Cancer Drug Resist. 2025-1-7

[10]
Single-cell RNA sequencing and machine learning provide candidate drugs against drug-tolerant persister cells in colorectal cancer.

Biochim Biophys Acta Mol Basis Dis. 2025-3

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