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Part of the IL-1 cytokine superfamily, the IL-36 family was discovered in the early 2000s due to the homology of its member sequences to the IL-1 cytokines. As pro- and anti-inflammatory cytokines, respectively, IL-36\u03b1, IL-36\u03b2, IL-36\u03b3 and IL-38 aid in maintaining homoeostasis by reciprocally regulating the body\u2019s response to damage and disease through IL-36R-associated signalling. With the significant roles of IL-36\u03b1, IL-36\u03b2 and IL-36\u03b3 in regulating the immune response realised, interest has grown in investigating their roles in cancer. While initial studies indicated solely tumour-suppressing roles, more recent work has identified tumour-promoting roles in cancer, suggesting a more complex dual functionality of the IL-36 cytokines. The activity of IL-38 in cancer is similarly complex, with the receptor antagonist displaying distinct tumour-suppressive roles, particularly in colorectal cancer (CRC), in addition to broad tumour-promoting roles in various other malignancies. This review provides a comprehensive overview of the IL-36 and IL-38 cytokines, their activation and IL-36R signalling, the physiological functions of these cytokines, and their activity in cancer.<\/jats:p>","DOI":"10.1038\/s41388-025-03293-4","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T23:35:26Z","timestamp":1741390526000},"page":"851-861","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The complex roles of IL-36 and IL-38 in cancer: friends or foes?"],"prefix":"10.1038","volume":"44","author":[{"given":"M\u00e9abh","family":"Finucane","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9214-149X","authenticated-orcid":false,"given":"Elizabeth","family":"Brint","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1362-5256","authenticated-orcid":false,"given":"Aileen","family":"Houston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,8]]},"reference":[{"key":"3293_CR1","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1006\/geno.2002.6752","volume":"79","author":"SL Taylor","year":"2002","unstructured":"Taylor SL, Renshaw BR, Garka KE, Smith DE, Sims JE. 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