{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:08:29Z","timestamp":1778645309825,"version":"3.51.4"},"reference-count":85,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tumor tissue is surrounded by mast cells (MCs), which participate in the inflammatory immune response by producing cytokines, proteases, and other molecules. MCs are involved in both innate and acquired immunity and are associated with the IgE response through the Fc\u03b5RI receptor. MCs mediate inflammation in several immune reactions, including acute hyperreactivity, leukocyte recruitment, acute tissue swelling, anaphylaxis, and pro-inflammatory cytokine production. They not only function as pro-inflammatory effector cells but may also contribute to the regulation of the acquired immune response in tumor tissue. Therefore, MCs may mediate immunity in breast cancer by promoting remodelling and counteracting cancer growth. They also produce anti-inflammatory substances, such as histamine, transforming growth factor-\u03b2 (TGF-\u03b2)1, IL-10, and IL-4, which inhibit the acquired immune response and reduce the inflammatory state. IL-37 and IL-38 are novel natural regulators of inflammation and are anti-inflammatory members of the IL-1 family. IL-1, generated by immune cells such as macrophages and lymphocytes, is released downstream of oncogenes in breast cancer, triggering an inflammatory response by stimulating other pro-inflammatory cytokines such as IL-6, tumor necrosis factor (TNF), and IL-33 (an early warning cytokine). Therefore, blocking IL-1 with IL-37 or IL-38 could represent a novel therapeutic strategy that, when combined with other treatments, could be beneficial in breast cancer. This review focuses on the new discoveries and insights into the role of MCs in breast cancer. We also analyzed molecules that can promote tumor growth and those that can inhibit cancer development and metastasis. This review aims to study the role of MCs accumulated in the stroma of breast adenocarcinoma in relation to secreted anti-inflammatory cytokines, such as IL-37 and IL-38.<\/jats:p>","DOI":"10.3390\/ijms27020824","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:01:14Z","timestamp":1768388474000},"page":"824","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mast Cells Accumulate in the Stroma of Breast Adenocarcinoma and Secrete Pro-Inflammatory Cytokines and Tumor-Damaging Mediators: Could IL-37 and IL-38 Play an Anti-Tumor Role?"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9475-4924","authenticated-orcid":false,"given":"Pio","family":"Conti","sequence":"first","affiliation":[{"name":"Immunology Division, Postgraduate Medical School, University of Chieti, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-8603","authenticated-orcid":false,"given":"Carla E.","family":"Gallenga","sequence":"additional","affiliation":[{"name":"Section of Ophthalmology, Department of Biomedical Sciences and Specialist Surgery, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6644-2773","authenticated-orcid":false,"given":"Ciro","family":"Annicchiarico","sequence":"additional","affiliation":[{"name":"Independent Researcher, 74023 Grottaglie, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armando","family":"Coppola","sequence":"additional","affiliation":[{"name":"Private Practice, Studio Armando Coppola, Corso Garibaldi 246, 80141 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5874-0376","authenticated-orcid":false,"given":"Raffaello","family":"Pellegrino","sequence":"additional","affiliation":[{"name":"Independent Researcher, Lecce-Castromediano\/Cavallino, Via S. Pelico 34, 73100 Lecce, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelangelo J.","family":"Conti","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, S. Andrea University \u201cLa Sapienza\u201d, 00189 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3746-5675","authenticated-orcid":false,"given":"Filiberto","family":"Mastrangelo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, School of Dentistry, University of Foggia, 71100 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Torgovnick, A., and Schumacher, B. (2015). DNA repair mechanisms in cancer development and therapy. Front. 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