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

Nature Communications
Bidesh MahataSarah A Teichmann

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.

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Citations

Mar 16, 2021·Molecular and Cellular Endocrinology·R M SlominskiR C Tuckey
May 1, 2021·Frontiers in Immunology·Emma L BishopSarah Dimeloe
May 1, 2021·International Journal of Molecular Sciences·Peter ErgangJiří Pácha
May 16, 2021·Nature Protocols·Lira MamanovaSarah A Teichmann
Jun 12, 2021·Nature Metabolism·Wael AbdrabouYoussef Idaghdour
Jul 20, 2021·Frontiers in Immunology·Arnold E PostlethwaiteAndrzej T Slominski
Jul 25, 2021·Cancer Research·Asmaa El-KenawiBrian Ruffell

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Datasets Mentioned

BETA
GSE19234

Methods Mentioned

BETA
flow cytometry
transgenic
ELISA
scRNAseq
scRNA-seq
ChIP-seq
FACS
RNAseq
transfection
PCR

Software Mentioned

MACS2
Bowtie
GraphPad Prism
Scanpy
UCSC genome browser
htseq
pySCENIC
UMAP
STAR

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