The role of γ-aminobutyric acid in tumor immunity
10.16438/j.0513-4870.2023-0461
- VernacularTitle:γ-氨基丁酸在肿瘤免疫中的作用
- Author:
Lu QIAO
;
Min XIAO
;
Jia-chun JIANG
;
Guo-hui WAN
- Publication Type:Research Article
- Keywords:
italic>γ-aminobutyric acid;
GABAergic system;
neoplasm;
immune system;
GABA receptor
- From:
Acta Pharmaceutica Sinica
2023;58(8):2120-2129
- CountryChina
- Language:Chinese
-
Abstract:
italic>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.
