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Tumors induce de novo steroid biosynthesis in T cells to evade immunity
Louise van der Weyden,
Nuno A Fonseca,
David J. Adams,
Jacqueline D. Shields,
Sarah A Teichmann
Posted 16 Nov 2018
bioRxiv DOI: 10.1101/471359
Posted 16 Nov 2018
Tumors subvert immune cell function to evade immune responses, and the mechanisms of tumor immune evasion are incompletely understood. Here we show that tumors induce de novo steroidogenesis in T lymphocytes to evade anti-tumor immunity. Using a novel transgenic fluorescent reporter mouse line we identify and characterize de novo steroidogenic T cells. Genetic ablation of T cell steroidogenesis restricts primary tumor growth and metastatic dissemination in mouse models. Steroidogenic T cells dysregulate anti-tumor immunity, which can be restored by inhibiting the steroidogenesis pathway. This study demonstrates that T cell de novo steroidogenesis is a cause of anti-tumor immunosuppression and a druggable target.
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