{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:21:00Z","timestamp":1788153660842,"version":"build-2803163510"},"reference-count":99,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017415","name":"Special Fund for Youth Clinical Research, Peking University First Hospital","doi-asserted-by":"publisher","award":["2021CR08"],"award-info":[{"award-number":["2021CR08"]}],"id":[{"id":"10.13039\/100017415","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The immunoglobulin E (IgE)\u2013Fc\u03b5RI axis, a central mediator of allergic inflammation, plays a dual role in cutaneous tumor immunity. Epidemiological evidence presents a paradox: atopic dermatitis (AD) promotes keratinocyte carcinogenesis, yet systemic allergic responses are associated with reduced melanoma risk. This review proposes the \u201cSkin AllergoOncology\u201d framework to resolve this paradox. The framework defines the skin as the only human organ in which two antagonistic IgE\u2013Fc\u03b5RI programs, protective immune surveillance and chronic pro-tumor inflammation, can be spatially juxtaposed. It is organized around three analytical dimensions: IgE repertoire quality, inflammatory kinetics, and effector-cell polarization state. We critically examine the epidemiological AD\u2013keratinocyte carcinoma association, highlighting the confounding role of immunosuppressive therapies, and review the molecular infrastructure enabling dual functional outputs, including antigen focusing by trimeric Fc\u03b5RI on Langerhans cells and microenvironment-dependent mast cell polarization. We contend that the absence of direct functional evidence for protective IgE in humans represents the central question for the next decade, and we propose a five-year dual-engine roadmap to identify the human protective IgE signature. This framework informs risk-stratified surveillance, engineered IgE antibody therapy, and the long-term oncological safety assessment of anti-allergic biologics.<\/jats:p>","DOI":"10.3390\/cancers18172807","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:24:03Z","timestamp":1788150243000},"page":"2807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Skin AllergoOncology: A Framework for Decoding the Context-Dependent Functions of the IgE\u2013Fc\u03b5RI Axis in Cutaneous Malignancies"],"prefix":"10.3390","volume":"18","author":[{"given":"Zhengkui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery and Burns, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery and Burns, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7627-4097","authenticated-orcid":false,"given":"Kun","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery and Burns, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/all.13119","article-title":"AllergoOncology\u2014The impact of allergy in oncology: EAACI position paper","volume":"72","author":"Bax","year":"2017","journal-title":"Allergy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/j.molmed.2022.06.003","article-title":"Molecular links between allergy and cancer","volume":"28","author":"Lorentz","year":"2022","journal-title":"Trends Mol. 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