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CARM1 Inhibition Enhances Cytotoxic T-cell Function and Sensitizes Resistant Cancers to Immune Attack

ABSTRACT: Several cancer drugs activate innate immune pathways in tumor cells but unfortunately compromise anti-tumor immune function. We discovered that inhibition of Carm1, an epigenetic enzyme, elicited beneficial effects in both cytotoxic T cells and tumor cells. Carm1 inactivation in cytotoxic T cells enhanced their activation state and anti-tumor function. In contrast, Carm1 inhibition in tumor cells resulted in genomic damage and activation of the cGAS-STING pathway. Inactivation of Med12, a regulatory component of the Mediator complex, elicited the same tumor cell phenotype, thereby connecting Carm1 to regulation of transcription. Inhibition of Carm1 induced potent T cell mediated tumor immunity and sensitized resistant, highly aggressive tumor cells to checkpoint blockade. The Carm1 – Med12 pathway thus offers an opportunity to enhance anti-tumor immunity while simultaneously sensitizing resistant tumor cells to immune attack.

ORGANISM(S): Mus musculus

PROVIDER: GSE144917 | GEO | 2022/01/31

REPOSITORIES: GEO

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