Work

Role of the neurotransmitter-receptor pathway in T-cell tumor immunology and cancer immunotherapy

Year: 2025

Type: article

Abstract: This review synthesizes how neurotransmitters-including glutamate, acetylcholine (ACh), γ-aminobutyric acid (GABA), serotonin (5-HT), and catecholamines-modulate T-cell immunity in the tumor microenvironment through activation, differentiation, trafficking, and checkpoint dependence. Glutamate amplifies T-cell receptor signaling but is counterbalanced by tumor-derived glutamate export. Cholinergic pathways exert dual effects through nicotinic and muscarinic receptors, whereas GABA generally imposes metabolic and signaling brakes that favor regulatory programs. Serotonin shows spatial divergence-suppressing peripheral responses but enhancing intratumoral cytotoxicity-and chronic β-adrenergic stress dampens effector function and limits immunotherapy efficacy. Advances in spatial multi-omics, single-cell profiling, and neuromodulation will help discover new targets across these axes. This review provides mechanistic insights and translational implications, highlighting emerging strategies such as glutamate receptor, metabotropic glutamate receptor 4 (mGluR4) or xCT (SLC7A11) inhibition, receptor subtype modulation, and β-blockade. Integrating neurotransmitter-receptor targeting with checkpoint inhibitors or cell therapies may improve the depth and durability of cancer immunotherapy.

Source: Acta Biochimica et Biophysica Sinica

DOI: 10.3724/abbs.2025216

Authors: Mingyu Fan, Xiang Zhao

Institutions: Chinese Academy of Sciences, Center for Excellence in Molecular Cell Science

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: National Natural Science Foundation of China, Chinese Academy of Sciences