{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:28:24Z","timestamp":1792787304637,"version":"4.5.0"},"reference-count":73,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"unspecified","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"UVA Cancer Biology Training Grant","award":["NIH T32CA009109"],"award-info":[{"award-number":["NIH T32CA009109"]}]},{"name":"UVA SEAS Endowed Graduate Fellowships","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"UVA Comprehensive Cancer Center Training Fellowship","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"UVA Jefferson Scholars Foundation Fellowship","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/04jmpmc14","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006599","name":"Focused Ultrasound Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100006599","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UVA Focused Ultrasound Immuno-Oncology (FUSION) Center","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"UVA Cancer Center Training Fellowship","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/04w75nz84","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DP5OD031846"],"award-info":[{"award-number":["DP5OD031846"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"US Department of Defense","award":["HT9425-25-1-0411"],"award-info":[{"award-number":["HT9425-25-1-0411"]}],"id":[{"id":"https:\/\/ror.org\/0447fe631","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30-CA044579"],"award-info":[{"award-number":["P30-CA044579"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UVA Wallace H. Coulter Foundation Translational Research grants","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/04cmszv87","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,7,11]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Focused ultrasound thermal ablation (T-FUS) is a clinically accessible, non-invasive modality capable of inducing rapid tumor cytoreduction while mobilizing early immunologic danger signals. However, its capacity to synergize with potent co-stimulatory immunotherapies in breast cancer (BC) remains undefined. Here, we investigated whether subtotal T-FUS cooperates with CD40 agonism to elicit durable, T cell-dependent tumor control across immunologically and molecularly distinct murine BC models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Subtotal ultrasound-guided T-FUS was applied to E0771, BRPKP110, EMT6, and 4T1 tumors in mice treated with systemic agonistic \u03b1CD40. Histology, ATP bioluminescence imaging, and multispectral flow cytometry were used to define acute tumor injury and immune remodeling. Therapeutic efficacy was evaluated by tumor growth, survival, T-cell depletion, and contralateral tumor rechallenge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Partial thermal ablation triggered canonical immunogenic cell-death signatures and acute remodeling of intratumoral myeloid populations, while expanding circulating CD4+ and\u2009CD8+ T cells. When layered onto this immunogenic milieu, \u03b1CD40 markedly constrained tumor outgrowth, yielding significant reductions in tumor burden across all models and complete tumor eradication in 30% of E0771 tumors, with additional complete responses in BRPKP110 and EMT6. Combination treatment also extended survival across three of four models. Efficacy required both CD4+ and\u2009CD8+ T cells, as depletion of either compartment abrogated tumor control. Complete responders mounted robust systemic immunity, rejecting contralateral tumor rechallenge with 100% protection and displaying persistent effector-memory T-cell activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Subtotal T-FUS cooperates with CD40 agonism to drive durable, T cell-dependent BC regression and immunologic memory. These findings establish T-FUS as an immune-potentiating partner for CD40 agonism and position this combination as a clinically scalable, in situ vaccination-like strategy with potential to broaden immunotherapy benefit across breast cancer subtypes, including luminal tumors that remain largely refractory to immune checkpoint blockade.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2026-015671","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:10:37Z","timestamp":1785845437000},"page":"e015671","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Focused ultrasound thermal ablation and CD40 agonism reprograms breast tumor immunity to drive regression and memory"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct04796220","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03237572","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03237572","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04796220","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03237572","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04796220","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03237572","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Zehra EF","family":"Demir","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aeryon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, 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O","family":"Maslova","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T","family":"Thede","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pouria","family":"Talebibarmi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, The George Washington University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R","family":"DeWitt","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA"},{"name":"Focused Ultrasound Immuno-Oncology Center, University of Virginia, Charlottesville, Virginia, 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