Role of the neurotransmitter-receptor pathway in T-cell tumor immunology and cancer immunotherapyOA
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 chronicβ-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,andβ-blockade.Integrating neurotransmitter-receptor targeting with checkpoint inhibitors or cell therapies may improve the depth and durability of cancer immunotherapy.
Mingyu Fan;Xiang Zhao
Key Laboratory of Multi-Cell Systems,Shanghai Institute of Biochemistry and Cell Biology,Center for Excellence in Molecular Cell Science,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,ChinaKey Laboratory of Multi-Cell Systems,Shanghai Institute of Biochemistry and Cell Biology,Center for Excellence in Molecular Cell Science,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China
医药卫生
celltumor microenvironmentneurotransmitterreceptor signalingcancer immunotherapyimmune checkpoint blockadeneuroimmune crosstalkimmunometabolism
《Acta Biochimica et Biophysica Sinica》 2026 (1)
P.67-89,23
supported by the grants from the National Key Research and Development Projects of the Ministry of Science and Technology of China(No.2024YFC2309200)the Strategic Priority Research Program of the Chinese Academy of Science(No.XDB0990000)the National Natural Science Foundation of China(No.82350107)the Independent Project of Shanghai Sci-Tech Inno Center for Infection&Immunity(No.ssIII-2024B01)the Shanghai Pujiang Program(No.23PJ1414300)the Hundred Talent Program by the Chinese Academy of Sciences,and the Start-up Funding from the Center for Excellence in Molecular Cell Science at the Chinese Academy of Sciences.
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