The immune system acts as a guardian of the host by initiating an immune response to harmful pathogens and tumor cells. However, overreaction is the cause of chronic or excessive inflammation and autoimmune diseases. Immune checkpoints play a key role in regulating the size of immune responses, thereby maintaining immune homeostasis and self-tolerance. However, tumor cells can also use immune checkpoints to evade immune surveillance, suppress anti-tumor immune responses, and ultimately lead to tumor genesis and tumor progression.
Recently, researchers from Qilu Medical College published an article entitled “Targeting RNA N6-methyladenosine to synergize with immune checkpoint therapy” in the journal Mol Cancer. In view of the key role of m6A modification in anti-tumor immunity, the researchers discussed the clinical significance of m6A targeted modification in improving the efficacy of immune checkpoint therapy for cancer control.
Immunocheckpoint therapy is a monoclonal antibody-based blocking agent that has revolutionized the field of cancer treatment. To date, various immune checkpoint inhibitors (ICIs) have been approved by the FDA for clinical use. However, low response rates, congenital or acquired drug resistance, and immunotherapy-related adverse events (irAEs) challenge the practicality of clinical applications. Therefore, finding new strategies that can be combined with ICI is crucial to maximizing treatment benefits.
In recent decades, m6A modification and the function of immune checkpoints have been extensively studied. It has been reported that a series of immune checkpoints are monitored in an m6A-dependent manner. In this review, the researchers introduced the biological effects of m6A modification and immune checkpoints, and described the latest progress in understanding the molecular mechanism behind m6A modification of immune checkpoints.
In order to verify the efficacy of m6A in clinical applications, researchers outlined the latest knowledge and future prospects of m6A modification in cancer treatment. In addition, recent attempts to combine targeted m6A modification with immune checkpoints as a promising collaborative strategy for cancer treatment, as well as potential limitations, were discussed.
In summary, research on m6A modification has brought new frontiers to cancer research, clarifying a comprehensive understanding of the epigenetic regulation of cancer, and providing additional insights into the molecular basis of tumorigenesis and immune response. Strategies that appropriately combine m6A-based therapy with ICI have enormous therapeutic potential. However, the mechanism by which m6A affects immune checkpoints is complex and not fully understood. Therefore, a better understanding of this phenomenon and improved patient selection criteria will significantly improve the outcome of combined therapy, which is worth further research.
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Reference
Xianyong Zhou et al. Targeting RNA N6-methyladenosine to synergize with immune checkpoint therapy. Mol Cancer. 2023 Feb 21;22(1):36. doi: 10.1186/s12943-023-01746-6.