Tumors induce de novo steroid biosynthesis in T cells to evade immunity

Mahata, Bidesh1,2; Pramanik, Jhuma2; van der Weyden, Louise2; Polanski, Krzysztof2; Kar, Gozde3,8; Riedel, Angela4; Chen, Xi5; Fonseca, Nuno A.3; Kundu, Kousik2,6; Campos, Lia S.2; Ryder, Edward2; Duddy, Graham2; Walczak, Izabela2; Okkenhaug, Klaus1; Adams, David J.2; Shields, Jacqueline D.4; Teichmann, Sarah A.2,7

2020-07-17

10.1038/s41467-020-17339-6

Nature Communications   影响因子和分区

2041-1723

Tumors subvert immune cell function to evade immune responses, yet the complex mechanisms driving immune evasion remain poorly understood. 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.

SCI

英语

NI期刊 ; NI论文

其他

CRUK Cancer Immunology fund[20193] ; ERC consolidator grant (ThDEFINE)[646794] ; Wellcome Sanger Institute[WT206194]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000552423000007

NATURE PUBLISHING GROUP

Web of Science

1.Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England
2.Wellcome Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England
3.EMBL European Bioinformat Inst, Wellcome Genome Campus, Cambridge CB10 1SD, England
4.Hutchison Med Res Council Res Ctr, Med Res Council Canc Unit, Cambridge, England
5.Southern Univ Sci & Technol, Dept Biol, Shenzhen, Peoples R China
6.Univ Cambridge, Dept Haematol, Cambridge Biomed Campus,Long Rd, Cambridge CB2 0PT, England
7.Cavendish Lab, Theory Condensed Matter, 19 JJ Thomson Ave, Cambridge CB3 0HE, England
8.AstraZeneca, Oncol R&D, Translat Med Res & Early Dev, Cambridge, England

Mahata, Bidesh,Pramanik, Jhuma,van der Weyden, Louise,et al. Tumors induce de novo steroid biosynthesis in T cells to evade immunity[J]. Nature Communications,2020,11(1).

Mahata, Bidesh.,Pramanik, Jhuma.,van der Weyden, Louise.,Polanski, Krzysztof.,Kar, Gozde.,...&Teichmann, Sarah A..(2020).Tumors induce de novo steroid biosynthesis in T cells to evade immunity.Nature Communications,11(1).

Mahata, Bidesh,et al."Tumors induce de novo steroid biosynthesis in T cells to evade immunity".Nature Communications 11.1(2020).