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| Home > Publications database > Early local immune activation following intra-operative radiotherapy in human breast tissue. |
| Home > Publications database > Early local immune activation following intra-operative radiotherapy in human breast tissue. |
| Journal Article | DKFZ-2026-00799 |
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2026
Taylor & Franics
Abingdon
Abstract: 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.
Keyword(s): Humans (MeSH) ; Breast Neoplasms: immunology (MeSH) ; Breast Neoplasms: radiotherapy (MeSH) ; Breast Neoplasms: surgery (MeSH) ; Breast Neoplasms: pathology (MeSH) ; Female (MeSH) ; Cytokines: metabolism (MeSH) ; Middle Aged (MeSH) ; Mastectomy, Segmental (MeSH) ; Immunity, Innate: radiation effects (MeSH) ; Adult (MeSH) ; Aged (MeSH) ; Radiotherapy, Adjuvant (MeSH) ; Breast: immunology (MeSH) ; Breast: radiation effects (MeSH) ; Breast cancer ; IL-3 ; Intra-operative radiotherapy (IORT) ; MIF ; eosinophils ; immune cell recruitment ; innate immune cells ; monocytes ; plasmacytoid dendritic cells ; Cytokines
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