Immunomodulatory Effect of Ultrasound-Guided Cryoablation in Early Breast Cancer: Pilot Study on blood and surgical samples

Background Cryoablation, a minimally invasive, image-guided procedure, induces tumor necrosis through freezing/thawing cycles. 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. Materials and methods 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 2–3 (T1), 2–3 weeks post-ablation (T2), and post-surgery (T3). Immune cell populations, including Tregs and activated CD137 T cells, were analyzed via flow cytometry. Serum HMGB1 and cytokines (e.g., IL-1β, IL-6, and TNF-α) were measured using Luminex assays. The histopathological analysis assessed the tumor response to ablation and immune infiltrates. Results Cryoablation significantly increased circulating HMGB1 levels at T1 (p = 0.047), with further elevation post-surgery (p = 0.023), suggesting immune activation. CD137 T cells, predominantly the CD4 subset, decreased significantly after surgery (p = 0.025), correlating with reduced interleukin-4 levels. Proliferating Tregs (Ki67 ) also declined after the combined treatment (p = 0.046). Histopathology confirmed complete tumor ablation in 9 of 10 cases, with immune infiltrates, predominantly CD3 lymphocytes (CD4 and CD8 equally represented). Conclusion Cryoablation induces significant immunological changes, including the release of HMGB1, modulation of CD137 T cells, and decreased Treg proliferation, highlighting its potential as both local and systemic immunomodulatory therapy. Relevance statement Cryoablation triggers immune activation in early BC, as indicated by increased CD137 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.