Pharmacologic RNA splicing modulation: a novel mechanism to enhance neoantigen-directed anti-tumor immunity and immunotherapy response

摘要: A recent study by Lu et al. 1 suggests a novel approach to increasing responsiveness to immune checkpoint blockade (ICB) therapy. ICB is a promising form of cancer immunotherapy that aims to boost the anti-tumoral immune response. This response is primarily driven by the presentation of different types of antigens at the cancer cell membrane via the type I major histocompatibility complex (MHC I). Neoantigens are tumor-specific antigens that are small (mostly 9-mers) mutated peptides that generally result from somatic mutations. High tumor mutational burden, which results in the formation of many neoantigens, is currently one of the main biomarkers for ICB response prediction. Because ICB is only effective in a minority of patients, new therapeutic strategies are required to augment this response. The authors of the study, published in Cell, 1 provide preclinical evidence that pharmacological modulation of the …