Inhibiting Type I arginine methyltransferase activity promotes the T cell mediated antitumor immune response
Menée à l'aide de lignées cellulaires, de modèles murins et de données de séquençage du projet "The Cancer Genome Atlas", cette étude met en évidence l'intérêt d'inhiber l'activité de l'arginine méthyltransférase de type 1 pour favoriser la réponse antitumorale induite par les lymphocytes T
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, inhibition of Type I PRMT activity induced an interferon gene signature, amplified responses to interferon and innate immune signaling pathways, and decreased expression of the immunosuppressive cytokine VEGF. In immunocompetent mouse tumor models including a model of T cell exclusion, representing a common mechanism of PD1 resistance in humans, Type I PRMT inhibition increased T cell infiltration, produced durable responses dependent on CD8+ T cells and enhanced efficacy of anti-PD1 therapy. These data suggest Type I PRMT inhibition can potentiate an antitumor immunity in refractory settings.