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In inflammation\u2010associated malignancies such as colitis\u2010associated cancer (CAC) and metabolic dysfunction\u2013associated fatty liver disease\u2013related hepatocellular carcinoma (MAFLD\u2010HCC), sustained inflammatory signaling integrates tissue injury with oncogenic pathways to promote tumor initiation and progression. Importantly, these cancers arise through prolonged preneoplastic stages, during which dysregulated immune and inflammatory responses not only drive malignant transformation but also create opportunities for cancer prevention and early disease interception. CAC and MAFLD\u2010HCC share convergent mechanisms, including IL\u20106\/STAT3 and NF\u2010\u03baB activation, cytokine\u2010driven survival signaling, and cooperation with genetic alterations in APC, KRAS, and TP53. A critical but often underappreciated dimension of this process is the failure of endogenous immunoregulatory systems that normally restrain excessive inflammation. Among these, the negative regulator of immune cells TIPE2 plays an important role in limiting inflammatory signaling, and its reduced activity contributes to the persistence of a tumor\u2010promoting inflammatory microenvironment that supports both disease initiation and progression. This review synthesizes the shared inflammatory, immunologic, and microenvironmental mechanisms underpinning CAC and MAFLD\u2010HCC, with a particular emphasis on how impaired immune regulation drives the transition from chronic inflammation to cancer. We further highlight therapeutic and preventive strategies targeting inflammation\u2010driven pathways, underscoring the dual relevance of immune modulation for cancer prevention in chronic inflammatory disease and for the treatment of established malignancy.<\/jats:p>","DOI":"10.1111\/cas.70360","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:20:20Z","timestamp":1773188420000},"page":"1209-1222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting Inflammation and Immune Regulation in Chronic Inflammation Associated Cancers"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5441-5306","authenticated-orcid":false,"given":"Lawan","family":"Rabiu","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Shenzhen University Medical School  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzhu","family":"Chinn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Shenzhen University Medical School  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Shenzhen University Medical School  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yerkezhan","family":"Yerkinkazhina","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Shenzhen University Medical School  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Shenzhen University Medical School  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-6581","authenticated-orcid":false,"given":"Wei\u2010Guo","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Shenzhen University Medical School  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph18091406"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26199498"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.025"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-327736"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00107"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-300953"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15082389"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0044-z"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12060824"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.03.026"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-025-02031-6"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-013-2084-3"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-2623"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.183"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaf026"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17050784"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1558263"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-022-10028-4"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222312739"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.01.001"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1642436"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-024-02157-0"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2023.155771"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000535524"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2009.43"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sigtrans.2017.23"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.142"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.07.013"},{"key":"e_1_2_14_31_1","doi-asserted-by":"crossref","unstructured":"H.\u2010L.Ngan J. 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