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Accumulating evidence strongly indicates that these mechanisms not only alter cancer cell\u2010intrinsic properties but also mediate reciprocal interactions between cancer cells and the tumor microenvironment (TME). In the context of cancer cell\u2010intrinsic changes, epigenetic alterations contribute to cancer cell plasticity by regulating stemness, cell state transitions, and therapy resistance. In addition, epigenetic changes are a key driver of the establishment of a tumor\u2010supportive environment by modifying the states of TME components, including fibroblasts, macrophages, and myeloid\u2010derived suppressor cells. Epigenetic reprogramming in cancer cells and TME components is often induced by factors such as hypoxia and the secretion of exosomal long noncoding RNAs (lncRNAs), cytokines, and metabolites. In this review, we discuss various epigenetic mechanisms controlling cancer cell\u2010intrinsic states, cancer cell\u2013TME crosstalk, current epigenetic therapies, and future research directions that may lead to the discovery of new biomarkers and the development of effective epigenetic anticancer therapeutics.<\/jats:p>","DOI":"10.1002\/1878-0261.70321","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:40:02Z","timestamp":1787658002000},"page":"2510-2532","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling the epigenetic code in cancer cell\u2013tumor microenvironment crosstalk"],"prefix":"10.1002","volume":"20","author":[{"given":"Ji Hoon","family":"Park","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Korea Advanced Institute of Science and Technology (KAIST)  Daejeon Republic of 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