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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Pramanik, Jhuma 
van der Weyden, Louise 
Polanski, Krzysztof  ORCID logo  https://orcid.org/0000-0002-2586-9576
Kar, Gozde 

Abstract

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.

Description

Keywords

Animals, CD4-Positive T-Lymphocytes, Cell Line, Tumor, Cholesterol Side-Chain Cleavage Enzyme, Humans, Immune Evasion, Melanoma, Mice, Mice, Knockout, Steroids

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

11

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12022/5)