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This pilot study investigates the immunomodulatory effects of cryoablation in early breast cancer (BC) patients by analyzing blood and surgical samples, with a focus on T-cell subsets, regulatory T cells (Tregs), serum cytokines, and high-mobility group box 1 (HMGB1) levels.<\/jats:p>\n <\/jats:sec>\n \n Materials and methods<\/jats:title>\n \n Ten patients with early BC (cT1 cN0) underwent ultrasound-guided cryoablation using a cryoablation system followed by surgical resection. Peripheral blood mononuclear cells were isolated at four time points: pre-ablation (T0), day 2\u20133 (T1), 2\u20133 weeks post-ablation (T2), and post-surgery (T3). Immune cell populations, including Tregs and activated CD137\n +<\/jats:sup>\n T cells, were analyzed via flow cytometry. Serum HMGB1 and cytokines (\n e.g<\/jats:italic>\n ., IL-1\u03b2, IL-6, and TNF-\u03b1) were measured using Luminex assays. The histopathological analysis assessed the tumor response to ablation and immune infiltrates.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Cryoablation significantly increased circulating HMGB1 levels at T1 (\n p<\/jats:italic>\n \u2009=\u20090.047), with further elevation post-surgery (\n p<\/jats:italic>\n \u2009=\u20090.023), suggesting immune activation. CD137\n +<\/jats:sup>\n T cells, predominantly the CD4\n +<\/jats:sup>\n subset, decreased significantly after surgery (\n p<\/jats:italic>\n \u2009=\u20090.025), correlating with reduced interleukin-4 levels. Proliferating Tregs (Ki67\n +<\/jats:sup>\n ) also declined after the combined treatment (\n p<\/jats:italic>\n \u2009=\u20090.046). Histopathology confirmed complete tumor ablation in 9 of 10 cases, with immune infiltrates, predominantly CD3\n +<\/jats:sup>\n lymphocytes (CD4\n +<\/jats:sup>\n and CD8\n +<\/jats:sup>\n equally represented).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Cryoablation induces significant immunological changes, including the release of HMGB1, modulation of CD137\n +<\/jats:sup>\n T cells, and decreased Treg proliferation, highlighting its potential as both local and systemic immunomodulatory therapy.\n <\/jats:p>\n <\/jats:sec>\n \n Relevance statement<\/jats:title>\n \n Cryoablation triggers immune activation in early BC, as indicated by increased CD137\n +<\/jats:sup>\n T cells, reduced Tregs, elevated HMGB1, enhanced inflammatory cytokine release, and the presence of mild to intense inflammatory infiltrates in surgical samples. These findings suggest the potential efficacy of cryoablation in supporting immunotherapies in the treatment of BC.\n <\/jats:p>\n <\/jats:sec>\n \n Key Points<\/jats:title>\n \n \n \n Cryoablation is a promising nonsurgical treatment for early-stage BC.<\/jats:p>\n <\/jats:list-item>\n \n The procedure may induce immune activation by increasing HMGB1 and modulating T-cell populations.<\/jats:p>\n <\/jats:list-item>\n \n Tregs appear to decrease after cryoablation, suggesting immunomodulatory potential.<\/jats:p>\n <\/jats:list-item>\n \n Histopathology confirms effective tumor ablation in most treated patients.<\/jats:p>\n <\/jats:list-item>\n \n Cryoablation shows immunomodulatory effects and may provide a rationale for future combination with immunotherapy.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Graphical Abstract<\/jats:title>\n <\/jats:sec>","DOI":"10.1186\/s41747-025-00655-1","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T09:24:35Z","timestamp":1766395475000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunomodulatory effect of ultrasound-guided cryoablation in early breast cancer: pilot study on blood and surgical samples"],"prefix":"10.1186","volume":"9","author":[{"given":"Federica","family":"Pediconi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Galati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Nuti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1781-3174","authenticated-orcid":false,"given":"Veronica","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Botticelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Tuosto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Pace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelia","family":"Rughetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"d\u2019Amati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Cerbelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Napoletano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"655_CR1","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/s41571-021-00514-z","volume":"18","author":"I Soerjomataram","year":"2021","unstructured":"Soerjomataram I, Bray F (2021) Planning for tomorrow: global cancer incidence and the role of prevention 2020\u20132070. 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The remaining authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"124"}}