The role of YTHDF2 in anti-tumor immunity

RNA <i>N</i> ⁶-methyladenosine (m⁶A) modification has been identified as the most abundant RNA modification and plays crucial roles in both physiological and pathological processes. YTHDF2 was the first identified reader protein that can recognize m⁶A modification and recent studies also revealed its ability to bind 5-methylcytidine (m⁵C) modification. YTHDF2 shows a dual binding capacity to both m⁶A and m⁵C, which leads to opposite mRNA outcomes. Multiple studies have highlighted the critical roles of YTHDF2 in tumor development and tumor microenvironment. Emerging findings showed that YTHDF2 plays critical roles in immune regulation, impacting T cell, B cell, NK cell, macrophage, innate/adaptive anti-tumor immune responses, and T-cell based immunotherapy. Inhibitors have been developed to target YTHDF2, which showed potential efficacy in tumor treatment. Herein, we reviewed the molecular mechanism of YTHDF2 and its roles in tumors, immune cells, and tumor microenvironment.