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Tiefenthaller, A.* ; Brix, N.* ; Hennel, R.* ; Pazos, M.* ; Kost, B.* ; von Bodungen, V.* ; Rack, B.* ; Wuerstlein, R.* ; Frey, B.* ; Gaipl, U.S.* ; Hess J. ; Unger, K. ; Danko, B. ; Selmansberger, M. ; Zitzelsberger, H. ; Harbeck, N.* ; Belka, C.* ; Scheithauer, H.* ; Lauber, K.*

Early local immune activation following intra-operative radiotherapy in human breast tissue.

OncoImmunology 15:2653318 (2026)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The local immune effects of cancer radiotherapy remain poorly characterized in humans due to limited access to irradiated tissue. Mechanistic insights largely derive from preclinical models employing tumor-intact, neoadjuvant-like settings. Here, we present real-world immunoprofiling data from breast cancer patients undergoing breast-conserving surgery with (n = 20) or without (n = 29) intraoperative radiotherapy (IORT). Postoperative wound fluid samples were analyzed by flow cytometry, multiplex cytokine profiling, and bulk RNA-sequencing, alongside systemic immune monitoring in peripheral blood. IORT triggered rapid local accumulation of distinct innate immune cell subsets and cytokines mediating recruitment, activation, and innate-adaptive crosstalk, accompanied by systemic features consistent with emergency hematopoiesis. Transcriptomic profiling of wound fluid mononuclear cells revealed enrichment of proinflammatory IL-6-JAK/STAT3 signaling. In vitro, irradiation of primary breast tissue cells recapitulated key cytokine patterns and led to robust senescence induction, suggesting irradiated, senescent normal tissue cells as drivers of early immune activation in postsurgical radiotherapy. These data provide direct clinical evidence that radiotherapy shapes local and systemic immune responses, offering mechanistic insights with clear relevance for tumor immunology and the development of rational radiotherapy‒immunotherapy combination strategies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Breast Cancer ; Il-3 ; Intra-operative Radiotherapy (iort) ; Mif ; Eosinophils ; Immune Cell Recruitment ; Innate Immune Cells ; Monocytes ; Plasmacytoid Dendritic Cells; Cancer; Interleukin-3; Recognition; Irradiation
ISSN (print) / ISBN 2162-4011
e-ISSN 2162-402X
Zeitschrift OncoImmunology
Quellenangaben Band: 15, Heft: 1, Seiten: , Artikelnummer: 2653318 Supplement: ,
Verlag Taylor & Francis
Verlagsort Philadelphia
Begutachtungsstatus Peer reviewed
Förderungen Heuer-Stiftung
Bundesministerium fr Bildung, Forschung, Technologie und Raumfahrt
Deutsche Forschungsgemeinschaft
Elite Netzwerk Bayern