Targeting protein arginine methyltransferases to enhance cancer immunotherapy

Arginine methylation is a post-translational modification found on many proteins, including RNA-binding proteins, signaling molecules, histones, and heat shock proteins, where it can alter protein-protein and protein-nucleic acid interactions. Arginine methylation regulates many cellular pathways, including RNA metabolism, signal transduction, gene expression, cellular stress responses, DNA repair, and, more recently, innate immune sensing. Here, we discuss recent advances in innate immune sensing and the emerging role of arginine methylation in suppressing tumor immune visibility. We describe current knowledge of protein arginine methyltransferase (PRMT) inhibitors and degraders and their use from preclinical models to clinical trials, alone or in combination with other therapies, to reduce tumor progression and enhance the effectiveness of cancer immunotherapy.