{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:57:21Z","timestamp":1785430641899,"version":"3.56.0"},"reference-count":205,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["YCJJ20252106"],"award-info":[{"award-number":["YCJJ20252106"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"publisher","award":["503\/3-016-02\/503-31-001"],"award-info":[{"award-number":["503\/3-016-02\/503-31-001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"award":["503\/3-016-02\/503-31-001"],"award-info":[{"award-number":["503\/3-016-02\/503-31-001"]}],"id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Glioma, particularly glioblastoma (GBM), is characterized by a strongly immunosuppressive tumor microenvironment that limits durable therapeutic responses. This review examines two interacting regulatory aspects of this microenvironment: metabolic reprogramming and neurotransmitter signaling co-option. Metabolic reprogramming is characterized by Warburg-type aerobic glycolysis, lactate accumulation, nutrient competition, and epigenetic lactylation, which generate an acidic and metabolically restrictive niche that impairs cytotoxic immune populations. In parallel, neurotransmitter signaling co-option, particularly through glutamatergic and GABAergic pathways, can influence neuron\u2013glioma communication, microglial\/macrophage phenotypes, and selected lymphocyte functions. As direct evidence for bidirectional interactions between metabolic reprogramming and neurotransmitter signaling in glioma remains incomplete, this relationship is presented as a working neurometabolic framework rather than a fully resolved mechanism. Lactate-driven immunometabolic suppression and glutamatergic neuron\u2013glioma signaling currently have the strongest support from glioma-specific studies, whereas some GABAergic, serotonergic, and macrophage-metabolic mechanisms remain emerging or context-dependent. The review also considers how mechanism-guided patient stratification, metabolically optimized immunotherapy and mechanism-based combination strategies targeting defined metabolic and neurotransmitter pathways may help restore antitumor immune competence within the glioma microenvironment.<\/jats:p>","DOI":"10.3390\/biom16070956","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:06:34Z","timestamp":1782875194000},"page":"956","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Reprogramming and Neurotransmitter Signaling Co-Option in the Glioma Immune Microenvironment: Dual-Axis Regulation of Immunosuppression"],"prefix":"10.3390","volume":"16","author":[{"given":"Pengyu","family":"Zhao","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0395-5986","authenticated-orcid":false,"given":"Kamil","family":"Saramowicz","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0119-599X","authenticated-orcid":false,"given":"Angelika","family":"Adamus-Grabicka","sequence":"additional","affiliation":[{"name":"Department of Bioinorganic Chemistry, Medical University of Lodz, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7044-9696","authenticated-orcid":false,"given":"Joanna","family":"Sikora","sequence":"additional","affiliation":[{"name":"Department of Bioinorganic Chemistry, Medical University of Lodz, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9206-1203","authenticated-orcid":false,"given":"Wioletta","family":"Rozp\u0119dek-Kami\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"vdad009","DOI":"10.1093\/noajnl\/vdad009","article-title":"Tumor microenvironment in glioblastoma: Current and emerging concepts","volume":"5","author":"Sharma","year":"2023","journal-title":"Neuro-Oncol. 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