{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:32:04Z","timestamp":1786437124104,"version":"build-2736575974"},"reference-count":148,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Texas Tech University School of Veterinary Medicine Start-up Funds"},{"name":"Brain Drug Discovery Center"},{"name":"Rural Cancer Collaborative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Glioblastoma (GBM) is one of the most aggressive and treatment-resistant cancers, shaped by a tumor microenvironment (TME) that is both metabolically demanding and strongly immunosuppressive. GBM relies heavily on fatty acid (FA) metabolism to sustain growth of rapidly dividing tumor cells and survive metabolic stress. GBM cells enhance lipid uptake, activate sterol regulatory element-binding protein 1 (SREBP-1)-driven lipogenesis, store excess lipids in droplets to prevent toxicity, and depend on fatty acid oxidation (FAO) to generate adenosine triphosphate (ATP) and maintain redox balance, particularly under nutrient-limited conditions. GBM TME is also consistently enriched with regulatory T cells (Tregs), which maintain suppressive activity despite the nutrient restrictions that impair effector T cells (Teffs). In hypoxia and nutrient limitation within the TME, Tregs can adapt by using FAO, lactate oxidation, and OXPHOS, supported by forkhead box P3 (Foxp3)-dependent metabolic programming, cluster of differentiation 36 (CD36)-mediated FA uptake, and hypoxia-related signals. At the same time, programmed cell death protein 1 (PD-1)\/programmed death-ligand 1 (PD-L1) signaling reduces glycolytic activity in Teffs and contributes to metabolic dysfunction, while also supporting the stability of oxidative metabolism in Tregs. Evidence from pre-clinical and clinical studies suggests a possible association between Treg enrichment in GBM and reduced responsiveness to immune checkpoint inhibitors (ICIs), although this relationship is not yet fully defined. Overall, current findings point to FA metabolism as a shared metabolic axis that supports both tumor progression and Treg-mediated immune resistance. Targeting lipid-driven pathways may offer an opportunity to disrupt these advantages and improve the effectiveness of existing immunotherapies for GBM.<\/jats:p>","DOI":"10.3390\/cancers18162573","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:09:36Z","timestamp":1786435776000},"page":"2573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fatty Acid Metabolism Rewires Glioblastoma Progression and Treg-Mediated Immune Resistance"],"prefix":"10.3390","volume":"18","author":[{"given":"Nowreen Islam","family":"Chowdhury","sequence":"first","affiliation":[{"name":"School of Veterinary Medicine, Texas Tech University, Amarillo, TX 79106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8906-462X","authenticated-orcid":false,"given":"Hebatollah","family":"Ewida","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA"},{"name":"Brain Drug Discovery Center, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud Salama","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Jerry H. 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