PRMT3 Drives IDO1-Dependent Radioresistance and Immunosuppression by Promoting Kynurenine Metabolism in Non-Small Cell Lung Cancer.

ABSTRACT: Radioresistance is one of the primary causes of treatment failure in non-small cell lung cancer. In this study, we identified protein arginine methyltransferase-3 (PRMT3) within tumors as a critical mediator impairing both radiotherapy sensitivity and T-cell antitumor activity. In tumor cells, PRMT3 mediated arginine methylation of transcription factor TFAP2A, enhancing its binding to the indoleamine 2,3-dioxygenase 1 (IDO1) promoter. Methylated TFAP2A exhibited a prolonged half-life, increased nuclear localization, and enhanced dimer formation, which ultimately led to heightened IDO1 expression that enhanced synthesis of kynurenine (Kyn). The elevated Kyn production boosted radioresistance in tumor cells and suppressed the infiltration and function of CD8+ T cells by activating aryl hydro

SUBMITTER: Zhang S 

PROVIDER: S-EPMC12809119 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature