Targeting Type I arginine methyltransferase PRMT1 promotes the T cell mediated antitumor immune response

Type I protein arginine methyltransferases (PRMTs) have been implicated in human cancers and a Type I PRMT inhibitor, GSK3368715, has recently entered clinical trials in solid and hematological malignancies. In cancer cell lines, Type I PRMT inhibitors induce an interferon gene signature, amplified responses to interferon and innate immune signaling pathways, and decreased expression of the immunosuppressive cytokine VEGFA. In immunocompetent mouse tumor models, Type I PRMT inhibition increased T cell infiltration, produced durable responses dependent on CD8 T cells and enhanced efficacy of anti-PD1, including a model of T cell exclusion, representing a common mechanism of PD1 resistance in humans. These data suggest Type I PRMT inhibition can potentiate an anti-tumor immunity in refractory settings. Paired end sequenced RNA-seq data from 10 Non-small cell lung cancer cell lines. All cell lines listed here have been sequenced with 2 replicates, containing GSK3368712 (treated) and control (DMSO) samples.