γ-氨基丁酸在肿瘤免疫中的作用  

The role of γ-aminobutyric acid in tumor immunity

作　　者：乔璐 肖敏 蒋佳纯 万国辉 QIAO Lu;XIAO Min;JIANG Jia-chun;WAN Guo-hui(School of Pharmaceutical Science,Sun Yat-Sen University,Guangzhou 510006,China)

机构地区：[1]中山大学药学院,广东广州510006

出　　处：《药学学报》2023年第8期2120-2129,共10页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(82122069,82073869);广东省基础与应用基础研究基金(2021B1515020004);高校基本科研业务费创新团队项目(23yxqntd001)。

摘　　要：γ-氨基丁酸(γ-aminobutyric acid,GABA)是人体内重要的神经递质之一,具有抑制神经活动的作用。除了神经系统,GABA能系统的组成成分也被发现存在于免疫细胞和肿瘤细胞中,它们能够通过分泌GABA影响肿瘤微环境中的其他细胞,并通过生成琥珀酸参与三羧酸循环为肿瘤细胞提供能量。GABA受体(GABA receptors,GABARs)的激活是GABA参与调控抗肿瘤免疫反应的主要途径。GABA A型受体(GABAA receptors,GABAARs)的激活可抑制T细胞的活化和增殖,促进巨噬细胞向抗炎表型转化,并能促进肿瘤细胞的生长和迁移;而GABA B型受体(GABAB receptors,GABABRs)的激活则通常被认为能抑制癌细胞的迁移,诱导癌细胞的凋亡。总体来说,受体的活化能抑制免疫细胞,但对肿瘤细胞的作用存在不同。此外,GABA转运体(GABA transporters,GATs)的表达水平下调也与肿瘤的发展进程有关。目前认为,GABA代谢拮抗剂和GABA受体药物可能成为肿瘤的治疗药物,但临床应用仍有限。γ-Aminobutyric acid(GABA)is a crucial inhibitory neurotransmitter found in various cells in the human body.While the GABAergic system is typically associated with the nervous system,recent research has revealed that immune cells and tumor cells also express components of this system.In the tumor microenvironment(TME),GABA is secreted to act extracellularly on other cells.GABA is metabolized via the GABA shunt and is involved in the tricarboxylic acid(TCA)cycle by generating succinate,which can provide energy for tumor cells.Activation of GABA receptors(GABARs)is a major pathway through which GABA participates in the regulation of antitumor immune responses.The activation of GABA type A receptors(GABAARs)can inhibit the activation and proliferation of T cells,elicit anti-inflammatory macrophages,and promote tumor cell growth and migration,while activation of GABA type B receptors(GABABRs)is generally considered to inhibit cancer cell migration and induce cancer cell apoptosis.In general,receptor activation inhibits immune cells,but the effect on tumor cells varies.Additionally,the downregulation of the expression levels of GABA transporters(GATs)is involved in tumor progression.Although antagonists of GABA metabolism and drugs that act on GABA receptors are considered therapeutic drugs for tumors,there have been few clinical studies conducted on them.

关 键 词：Γ-氨基丁酸 γ-氨基丁酸能系统 肿瘤 免疫系统 Γ-氨基丁酸受体 

分 类 号：R966[医药卫生—药理学]