Cellular
immunotherapy has recently emerged as a fourth pillar in
cancer treatment co-joining surgery,
chemotherapy and
radiotherapy. Where, the discovery of immune checkpoint blockage or inhibition (ICB/ICI), anti-PD-1/PD-L1 and anti-CTLA4-based,
therapy has revolutionized the class of
cancer treatment at a different level. However, some
cancer patients escape this immune surveillance mechanism and become resistant to ICB-
therapy. Therefore, a more advanced or an alternative treatment is required urgently. Despite the functional importance of epitranscriptomics in diverse clinico-biological practices, its role in improving the efficacy of ICB
therapeutics has been limited. Consequently, our study encapsulates the evidence, as a possible strategy, to improve the efficacy of ICB-
therapy by co-targeting molecular checkpoints especially N6A-modification machineries which can be reformed into
RNA modifying drugs (RMD). Here, we have explained the mechanism of individual
RNA-modifiers (editor/writer, eraser/remover, and effector/reader) in overcoming the issues associated with high-dose antibody toxicities and drug-resistance. Moreover, we have shed light on the importance of suppressor of
cytokine signaling (SOCS/CISH) and
microRNAs in improving the efficacy of ICB-
therapy, with brief insight on the current
monoclonal antibodies undergoing clinical trials or already approved against several solid
tumor and metastatic
cancers. We anticipate our investigation will encourage researchers and clinicians to further strengthen the efficacy of ICB-
therapeutics by considering the importance of epitranscriptomics as a
personalized medicine.