{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:22:16Z","timestamp":1791490936414,"version":"4.3.4"},"reference-count":62,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T00:00:00Z","timestamp":1589846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Belgian Foundation against cancer.","award":["Mesothelioma call 2016-2020"],"award-info":[{"award-number":["Mesothelioma call 2016-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>For poorly immunogenic tumors such as mesothelioma there is an imperious need to understand why antigen-presenting cells such as dendritic cells (DCs) are not prone to supporting the anticancer T cell response. The tumor microenvironment (TME) is thought to be a major contributor to this DC dysfunction. We have reported that the acidic TME component promotes lipid droplet (LD) formation together with epithelial-to-mesenchymal transition in cancer cells through autocrine transforming growth factor-\u03b22 (TGF-\u03b22) signaling. Since TGF-\u03b2 is also a master regulator of immune tolerance, we have here examined whether acidosis can impede immunostimulatory DC activity. We have found that exposure of mesothelioma cells to acidosis promotes TGF-\u03b22 secretion, which in turn leads to LD accumulation and profound metabolic rewiring in DCs. We have further documented how DCs exposed to the mesothelioma acidic milieu make the anticancer vaccine less efficient in vivo, with a reduced extent of both DC migratory potential and T cell activation. Interestingly, inhibition of TGF-\u03b22 signaling and diacylglycerol O-acyltransferase (DGAT), the last enzyme involved in triglyceride synthesis, led to a significant restoration of DC activity and anticancer immune response. In conclusion, our study has identified that acidic mesothelioma milieu drives DC dysfunction and altered T cell response through pharmacologically reversible TGF-\u03b22-dependent mechanisms.<\/jats:p>","DOI":"10.3390\/cancers12051284","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T10:37:38Z","timestamp":1589971058000},"page":"1284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Acidosis-Induced TGF-\u03b22 Production Promotes Lipid Droplet Formation in Dendritic Cells and Alters Their Potential to Support Anti-Mesothelioma T Cell Response"],"prefix":"10.3390","volume":"12","author":[{"given":"Natalia","family":"Trempolec","sequence":"first","affiliation":[{"name":"Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), UCLouvain, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charline","family":"Degavre","sequence":"additional","affiliation":[{"name":"Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), UCLouvain, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9376-7654","authenticated-orcid":false,"given":"Bastien","family":"Doix","sequence":"additional","affiliation":[{"name":"Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), UCLouvain, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6499-9648","authenticated-orcid":false,"given":"Davide","family":"Brusa","sequence":"additional","affiliation":[{"name":"Institut de Recherche Exp\u00e9rimentale et Clinique (IREC) Flow Cytometry Platform, UCLouvain, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8795-9131","authenticated-orcid":false,"given":"Cyril","family":"Corbet","sequence":"additional","affiliation":[{"name":"Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), UCLouvain, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5360-0286","authenticated-orcid":false,"given":"Olivier","family":"Feron","sequence":"additional","affiliation":[{"name":"Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), UCLouvain, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/nrc.2017.42","article-title":"Novel insights into mesothelioma biology and implications for therapy","volume":"17","author":"Yap","year":"2017","journal-title":"Nat. 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