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

Published version
Peer-reviewed

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Authors

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

Abstract

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

Article, /631/67/327, /631/67/580, /38, /38/91, /13/31, /64/60, /38/77, /13/106, /9, /13/21, /13/1, article

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723

Volume Title

11

Publisher

Nature Publishing Group UK
Sponsorship
Cancer Research UK (CRUK) (20193, 20193)