Recent Advances of RNA m⁶A Modifications in Cancer Immunoediting and Immunotherapy

Cancer immunotherapy, which modulates immune responses against tumors using immune-checkpoint inhibitors or adoptive cell transfer, has emerged as a novel and promising therapy for tumors. However, only a minority of patients demonstrate durable responses, while the majority of patients are resistant to immunotherapy. The immune system can paradoxically constrain and promote tumor development and progression. This process is referred to as cancer immunoediting. The mechanisms of resistance to immunotherapy seem to be that cancer cells undergo immunoediting to evade recognition and elimination by the immune system. RNA modifications, specifically N⁶-methyladenosine (m⁶A) methylation, have emerged as a key regulator of various post-transcriptional gene regulatory processes, such as RNA export, splicing, stability, and degradation, which play unappreciated roles in various physiological and pathological processes, including immune system development and cancer pathogenesis. Therefore, a deeper understanding of the mechanisms by which RNA modifications impact the cancer immunoediting process can provide insight into the mechanisms of resistance to immunotherapies and the strategies that can be used to overcome such resistance. In this chapter, we briefly introduce the background of cancer immunoediting and immunotherapy. We also review and discuss the roles and mechanisms of RNA m⁶A modifications in fine-tuning the innate and adaptive immune responses, as well as in regulating tumor escape from immunosurveillance. Finally, we summarize the current strategies targeting m⁶A regulators for cancer immunotherapy.