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Its acute systemic immunogenic effects relative to BCS-only are not well characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Women with histologically confirmed breast carcinoma were allocated in an alternating 1:1 sequence to BCS\u2009+\u2009TARGIT-IORT or BCS-only groups. Peripheral blood was sampled pre-operatively and 24\u00a0h post-surgery. ICD and cytokine\/DAMP mediators, including HMGB1, PRF1, TRAIL, FASL-NFSF6, CASP-8, GZMB, CRT, TLR4, RAGE, GDF15, and M-CSF, were quantified using ELISA. Perioperative changes were analyzed using the Wilcoxon signed-rank test; between-group \u0394 differences were assessed using the Mann\u2013Whitney\n                      <jats:italic>U<\/jats:italic>\n                      test.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Forty-two patients were enrolled (26 BCS\u2009+\u2009TARGIT-IORT; 16 BCS-only). TARGIT-IORT induced a distinct early immune shift across ICD markers. HMGB1 showed the most pronounced change (3410.5\u2009\u2192\u2009359.8\u00a0pg\/ml;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), significantly greater than that after BCS-only (1040.7\u2009\u2192\u2009263.6\u00a0pg\/ml; \u0394\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). TRAIL (246.1\u2009\u2192\u2009155.5\u00a0pg\/ml;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) and FASL-NFSF6 (1087.1\u2009\u2192\u2009839.3\u00a0pg\/ml;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003) also declined significantly after TARGIT-IORT, whereas changes following BCS alone were modest. TARGIT-IORT increased M-CSF (266.7\u2009\u2192\u2009386.7\u00a0pg\/ml;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.037) and reduced TLR4 (1456.3\u2009\u2192\u20091331.3\u00a0ng\/ml;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007), with no significant perioperative changes in RAGE, GDF15, CRT, GZMB, or CASP-8.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Within 24\u00a0h, TARGIT-IORT generates a coordinated ICD-related and cytokine\/DAMP signature, marked HMGB1 depletion, death ligand modulation, TLR4 engagement, and M-CSF upregulation, consistent with rapid immune priming. These findings are exploratory and should be interpreted within a translational framework. Larger, randomized multicentre studies with extended longitudinal and tissue-level immune profiling are needed to confirm these signals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12094-026-04353-1","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T17:51:17Z","timestamp":1776448277000},"page":"4666-4682","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of HMGB1, PRF1, TRAIL, and M-CSF after TARGIT-IORT in breast-conserving surgery: defining a unique acute immune landscape"],"prefix":"10.1007","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6109-0140","authenticated-orcid":false,"given":"Yastira","family":"Ramdas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Worsley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter Willem","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol-Ann","family":"Benn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"issue":"12","key":"4353_CR1","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1200\/OP.21.00635","volume":"17","author":"C Shah","year":"2021","unstructured":"Shah C, Al-Hilli Z, Vicini F. 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