Reshaping the tumor microenvironment by N6-methyladenosine: advances, implications, and prospects

Tumors employ diverse mechanisms to reshape the tumor microenvironment (TME), leading to immune escape and therapeutic resistance. A key mechanism underlying this reshaping is epigenetic alterations, such as DNA modification, RNA modification, histone modification, chromatin remodeling, and non-coding RNA regulation. Among these, N6-methyladenosine (m6A), the most prevalent internal chemical modification in eukaryotic mRNA, exerts crucial roles in numerous physiological and pathological processes, including tumorigenesis. Divergent m6A modifications have been demonstrated in various tumors, influencing nearly every stage of tumor development. Furthermore, emerging evidence suggests that m6A modifications also serve as key determinants in regulating the TME. This review generalizes recent advances on the role of how m6A modifications reshape the TME, focusing on immune cells, stromal cells, and non-cellular compositions, and discusses the potential implications for cancer therapy. Deciphering the biological logic by which m6A modifications reshape the TME will offer promising strategies for cancer prevention and treatment.