N6-methyladenosine RNA modification in PD-1/PD-L1: Novel implications for immunotherapy

Abstract

Cancer immunotherapy has been shown to achieve significant antitumor effects in a variety of malignancies. Out of all the immune checkpoint molecules, PD-1/PD-L1 inhibitor therapy has achieved great success. However, only some cancer patients benefit from this treatment strategy owing to drug resistance. Therefore, identifying the underlying modulators of the PD-1/PD-L1 pathway to completely comprehend the mechanisms of anti-PD-1/PD-L1 treatment is crucially important. Recent research has validated that m6A modification plays a critical role in the PD-1/PD-L1 axis, thus regulating the immune response and immunotherapy strategies. In this review, we summarized the latest research on the regulation of m6A modification in PD-1/PD-L1 pathways in cancer proliferation, invasion, and prognosis based on different kinds of cancers and discussed the possible mechanisms. We also reviewed m6A-associated lncRNAs in the regulation of the PD-1/PD-L1 pathway. More importantly, we outlined the influence of m6A modulation on anti-PD-1 therapy and m6A-related molecules that could predict the curative effect of anti-PD-1/PD-L1 therapy. Further studies exploring the definitive regulation of m6A on the PD1/PD-1 pathway and immunotherapy are needed, which may address some of the current limitations in immunotherapy.

Keywords: Cancer; Immunotherapy; PD-1; PD-L1; m6A methylation.