Journal Article

DKFZ-2025-01699

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Photon and particle radiotherapy induce redundant modular chemotaxis of human lymphocytes.

Kraske, J. (First author)DKFZ* ; Allers, M. M.DKFZ* ; Smirnov, A.DKFZ* ; Lenoir, B.DKFZ* ; Ahmed, A.DKFZ* ; Suarez-Carmona, M.DKFZ* ; Hampel, M.DKFZ* ; Krunic, D.DKFZ* ; Tietz-Dalfuß, A.DKFZ* ; Beikert, T.DKFZ* ; Schneeweiss, J. M.DKFZ* ; Brons, S. ; Albrecht, D.DKFZ* ; Trinh, T.DKFZ* ; Liu, M.DKFZ* ; Giese, N.DKFZ* ; Glowa, C.DKFZ* ; Liermann, J. ; Lopez Perez, R.DKFZ* ; Jäger, D.DKFZ* ; Debus, J.DKFZ* ; Halama, N.DKFZ* ; Huber, P. (Last author)DKFZ* ; Walle, T. (Last author)DKFZ*

2025
JCI Insight Ann Arbor, Michigan

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Please use a persistent id in citations: doi:10.1172/jci.insight.190149

Abstract: Radiotherapy triggers chemokine release and leukocyte infiltration in pre-clinical models through activation of the senescence-associated secretory phenotype (SASP). However, effects of irradiation on senescence and SASP in human tissue and in the context of particle radiotherapy remain unclear. Here, we analyzed chemokine patterns after radiotherapy of human pancreatic tumors and cancer cell lines. We show that irradiated tumor cells co-express SASP chemokines in defined modules. These chemokine modules correlated with infiltration of distinct leukocyte subtypes expressing cognate receptors. We developed a patient-derived pancreatic tumor explant system, which confirmed our identified radiation-induced chemokine modules. Chemokine modules were partially conserved in cancer cells in response to photon and particle irradiation showing a dose-dependent plateau effect and induced subsequent migration of NK and T cell populations. Hence, our work reveals redundant interactions of cancer cells and immune cells in human tissue, suggesting that targeting multiple chemokines is required to efficiently perturb leukocyte infiltration after photon or particle radiotherapy.

Keyword(s): Cellular senescence ; Chemokines ; Immunology ; Oncology ; Radiation therapy

Note: #EA:E055#LA:E055# / 2025 Aug 14;10(18):e190149

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Contributing Institute(s):

1. E055 KKE Molekulare Radioonkologie (E055)
2. Angewandte Tumor-Immunität (D120)
3. Translationale Immuntherapie (D196)
4. Lichtmikroskopie (W210)
5. E040 Med. Physik in der Strahlentherapie (E040)
6. E050 KKE Strahlentherapie (E050)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2025

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Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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