{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:19:56Z","timestamp":1787807996073,"version":"build-2784847793"},"reference-count":85,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ten\u2010Eleven Translocation 2 (TET2) is an Fe(II)\u2010 and \u03b1\u2010ketoglutarate\u2010dependent dioxygenase that initiates active DNA demethylation by oxidizing 5\u2010methylcytosine (5mC). Beyond this enzymatic role, TET2 links DNA methylation dynamics with chromatin regulation, cellular metabolism, immune\u2010cell identity, and treatment response in a context\u2010dependent manner. Loss\u2010of\u2010function mutations in TET2 are among the most frequent genetic events in age\u2010related clonal hematopoiesis of indeterminate potential (CHIP), where they are associated with higher risks of hematological malignancies and cardiovascular disease. Human genetic and clinical studies support these associations, while experimental models suggest that mutant hematopoietic clones can promote myeloid inflammatory programs through enhancer remodeling, NLRP3 inflammasome activation, IL\u20101\u03b2\/IL\u20106 signaling, and altered inflammatory resolution. In solid tumors and cancer therapy, TET2 has more variable effects: tumor\u2010cell\u2010intrinsic TET2 loss can contribute to immune escape or therapeutic resistance in selected settings, whereas TET2 disruption in engineered T cells can enhance memory\u2010like persistence and anti\u2010tumor activity, with possible long\u2010term oncogenic risk. This narrative, mechanism\u2010oriented review integrates current evidence on TET2 biology across clonal hematopoiesis, inflammation, cancer, and immunotherapy. We focus on evidence level, cell type, direction of TET2 alteration, and metabolic or therapeutic context as determinants of divergent TET2 functions. TET2 has traditionally been described as a DNA demethylation enzyme, but recent studies increasingly place it among context\u2010dependent regulators of immune and disease phenotypes. The unresolved issue is why TET2 loss, inhibition, activation, or engineered deletion can produce distinct, and sometimes opposing, effects in hematopoietic stem\/progenitor cells, macrophages, tumor cells, neurons, microglia, and CAR\u2010T cells. This review uses four variables\u2014cell type, direction of alteration, functional layer, and microenvironmental or therapeutic context\u2014to interpret evidence from CHIP, hematologic malignancies, cardiovascular inflammation, solid tumors, and immunotherapy.<\/jats:p>","DOI":"10.1002\/cbf.70287","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:53:32Z","timestamp":1787036012000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TET2 as a Context\u2010Dependent Epigenetic Integrator in Clonal Hematopoiesis, Inflammation, Cancer, and Immunotherapy"],"prefix":"10.1002","volume":"44","author":[{"given":"XiaoJie","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine Affiliated Hospital of Jiaxing University, The First Hospital of Jiaxing Jiaxing City 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Jiaxing Jiaxing City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5369-4073","authenticated-orcid":false,"given":"Dekuai","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Radiology Affiliated Hospital of Jiaxing University, The First Hospital of Jiaxing Jiaxing City 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