Targeting RNA N6-methyladenosine to synergize with immune checkpoint therapy

Abstract

Cancer immunotherapy, especially immune checkpoint therapy, has revolutionized therapeutic options by reactivating the host immune system. However, the efficacy varies, and only a small portion of patients develop sustained antitumor responses. Hence, illustrating novel strategies that improve the clinical outcome of immune checkpoint therapy is urgently needed. N6-methyladenosine (m⁶A) has been proved to be an efficient and dynamic posttranscriptional modification process. It is involved in numerous RNA processing, such as splicing, trafficking, translation and degradation. Compelling evidence emphasizes the paramount role of m⁶A modification in the regulation of immune response. These findings may provide a foundation for the rational combination of targeting m⁶A modification and immune checkpoints in cancer treatment. In the present review, we summarize the current landscape of m⁶A modification in RNA biology, and highlight the latest findings on the complex mechanisms by which m⁶A modification governs immune checkpoint molecules. Furthermore, given the critical role of m⁶A modification in antitumor immunity, we discuss the clinical significance of targeting m⁶A modification to improve the efficacy of immune checkpoint therapy for cancer control.