{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:45Z","timestamp":1787027865587,"version":"build-2736575974"},"reference-count":205,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1D1A1B07048567"],"award-info":[{"award-number":["2018R1D1A1B07048567"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["SRC-2017R1A5A1014560"],"award-info":[{"award-number":["SRC-2017R1A5A1014560"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells10092250","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T11:01:37Z","timestamp":1630321297000},"page":"2250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISH"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8323-2525","authenticated-orcid":false,"given":"Sunil","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, Korea"},{"name":"Science Research Center (SRC) for Immune Research on Non-lymphoid Organ (CIRNO), Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parth","family":"Sarthi","sequence":"additional","affiliation":[{"name":"University Department of Botany, M.Sc. Biotechnology, Ranchi University, Ranchi 834008, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7690-5517","authenticated-orcid":false,"given":"Indra","family":"Mani","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Gargi College, University of Delhi, New Delhi 110049, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8372-9424","authenticated-orcid":false,"given":"Muhammad Umer","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, Korea"},{"name":"Science Research Center (SRC) for Immune Research on Non-lymphoid Organ (CIRNO), Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myeong-Ho","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, Korea"},{"name":"Science Research Center (SRC) for Immune Research on Non-lymphoid Organ (CIRNO), Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science, Dayananda Sagar University, Bengaluru 560078, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2233-9449","authenticated-orcid":false,"given":"Yong-Soo","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, Korea"},{"name":"Science Research Center (SRC) for Immune Research on Non-lymphoid Organ (CIRNO), Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"ref_1","first-page":"A204","article-title":"333 Targeting the apical intracellular checkpoint CISH unleashes T cell neoantigen reactivity and effector program","volume":"8","author":"Palmer","year":"2020","journal-title":"J. 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