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Here we show that tumors induce de novo steroidogenesis in T lymphocytes to evade anti-tumor immunity. Using a transgenic steroidogenesis-reporter mouse line we identify and characterize de novo steroidogenic immune cells, defining the global gene expression identity of these steroid-producing immune cells and gene regulatory networks by using single-cell transcriptomics. Genetic ablation of T cell steroidogenesis restricts primary tumor growth and metastatic dissemination in mouse models. Steroidogenic T cells dysregulate anti-tumor immunity, and inhibition of the steroidogenesis pathway is sufficient to restore anti-tumor immunity. This study demonstrates T cell de novo steroidogenesis as a mechanism of anti-tumor immunosuppression and a potential druggable target.<\/jats:p>","DOI":"10.1038\/s41467-020-17339-6","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T10:23:54Z","timestamp":1594981434000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Tumors induce de novo steroid biosynthesis in T cells to evade immunity"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4506-0184","authenticated-orcid":false,"given":"Bidesh","family":"Mahata","sequence":"first","affiliation":[]},{"given":"Jhuma","family":"Pramanik","sequence":"additional","affiliation":[]},{"given":"Louise","family":"van der Weyden","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-9576","authenticated-orcid":false,"given":"Krzysztof","family":"Polanski","sequence":"additional","affiliation":[]},{"given":"Gozde","family":"Kar","sequence":"additional","affiliation":[]},{"given":"Angela","family":"Riedel","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2648-3146","authenticated-orcid":false,"given":"Xi","family":"Chen","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-578X","authenticated-orcid":false,"given":"Nuno A.","family":"Fonseca","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1019-8351","authenticated-orcid":false,"given":"Kousik","family":"Kundu","sequence":"additional","affiliation":[]},{"given":"Lia S.","family":"Campos","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1799-9899","authenticated-orcid":false,"given":"Edward","family":"Ryder","sequence":"additional","affiliation":[]},{"given":"Graham","family":"Duddy","sequence":"additional","affiliation":[]},{"given":"Izabela","family":"Walczak","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9432-4051","authenticated-orcid":false,"given":"Klaus","family":"Okkenhaug","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9490-0306","authenticated-orcid":false,"given":"David J.","family":"Adams","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2153-9710","authenticated-orcid":false,"given":"Jacqueline D.","family":"Shields","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6294-6366","authenticated-orcid":false,"given":"Sarah A.","family":"Teichmann","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,7,17]]},"reference":[{"key":"17339_CR1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1210\/er.2010-0013","volume":"32","author":"WL Miller","year":"2011","unstructured":"Miller, W. 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