Targeting PRMT3 for HCC antitumor immunity

Targeting PRMT3, an arginine methyltransferase that is upregulated by T cells in response to immune checkpoint therapy and promotes immunotherapy resistance, could help treat hepatocellular carcinoma (HCC) by decreasing methylation of the mitochondrial homeostasis regulator HSP60, resulting in mitochondrial DNA leakage that activates a cGAS/STING mediated innate immune response.

In bioinformatic analyses of public HCC patient data sets, PRMT3 mRNA expression was increased in HCC tumors compared with normal adjacent tissue, and higher PRMT3 expression was negatively correlated with overall survival and expression of a cytotoxic CD8⁺ T cell mRNA signature in tumors...