Targeting RNA N⁶-methyladenosine modification: a precise weapon in overcoming tumor immune escape

Immunotherapy, especially immune checkpoint inhibitors (ICIs), has revolutionized the treatment of many types of cancer, particularly advanced-stage cancers. Nevertheless, although a subset of patients experiences dramatic and long-term disease regression in response to ICIs, most patients do not benefit from these treatments. Some may even experience cancer progression. Immune escape by tumor cells may be a key reason for this low response rate. N⁶-methyladenosine (m⁶A) is the most common type of RNA methylation and has been recognized as a critical regulator of tumors and the immune system. Therefore, m⁶A modification and related regulators are promising targets for improving the efficacy of tumor immunotherapy. However, the association between m⁶A modification and tumor immune escape (TIE) has not been comprehensively summarized. Therefore, this review summarizes the existing knowledge regarding m⁶A modifications involved in TIE and their potential mechanisms of action. Moreover, we provide an overview of currently available agents targeting m⁶A regulators that have been tested for their elevated effects on TIE. This review establishes the association between m⁶A modifications and TIE and provides new insights and strategies for maximizing the efficacy of immunotherapy by specifically targeting m⁶A modifications involved in TIE.