Epigenetic reprogramming of T cell metabolism restores function and enhances anti-tumor immunity in lung cancer - PubMed
2 hours ago
- #lung cancer immunotherapy
- #epigenetics
- #T cell exhaustion
- Epigenetic drug screen identifies bromodomain and extra-terminal motif inhibitors (BETis) as enhancers of effector functions in exhausted T cells from lung cancer patients.
- BETis reinvigorate T cells by activating the polyamine biosynthesis pathway, expanding polyamine pools, and altering chromatin accessibility via the MYC-ODC axis.
- Inhibition of ornithine decarboxylase (ODC1) abolishes BETi-mediated immunopotentiation, highlighting its key role in this epigenetic-metabolic reprogramming.
- BETis reduce terminally exhausted T cells and promote progenitor exhausted T cells, enhancing T cell plasticity and anti-tumor immunity.
- BETi treatment or adoptive transfer of BETi-treated T cells suppresses malignant pleural effusion formation in a lung cancer model.