Photon and particle radiotherapy induce redundant modular chemotaxis of human lymphocytes
Radiotherapy triggers chemokine release and leukocyte infiltration in preclinical 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 coexpressed 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 verified 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.
Authors
- Ramon Lopez Perez (ORCID: https://orcid.org/0000-0002-6876-2074)
- Dorothee Albrecht (ORCID: https://orcid.org/0000-0002-4821-1005)
- Stephan Brons (ORCID: https://orcid.org/0000-0002-4695-0816)
- Dirk Jäger
- Thomas Walle (ORCID: https://orcid.org/0000-0003-4835-955X)
- Jakob Liermann (ORCID: https://orcid.org/0000-0002-1445-1940)
- Mareike Hampel (ORCID: https://orcid.org/0009-0007-0756-8378)
- Bénédicte Lenoir (ORCID: https://orcid.org/0000-0002-3540-9688)
- Tizian Beikert
- Nathalia A. Giese (ORCID: https://orcid.org/0000-0001-5920-3142)
- Aleksei Smirnov (ORCID: https://orcid.org/0009-0009-3334-9085)
- Damir Krunic (ORCID: https://orcid.org/0000-0002-5615-627X)
- Meggy Suarez‐Carmona (ORCID: https://orcid.org/0000-0002-8892-1546)
- Azaz Ahmed (ORCID: https://orcid.org/0000-0003-3000-7951)
- Christin Glowa (ORCID: https://orcid.org/0000-0002-5557-9799)
- Niels Halama (ORCID: https://orcid.org/0000-0003-0344-6027)
- Alexandra Tietz-Dalfuß
- Jürgen Debus (ORCID: https://orcid.org/0000-0002-6411-4811)
- Peter E. Huber (ORCID: https://orcid.org/0000-0002-4811-300X)
- Joscha A. Kraske (ORCID: https://orcid.org/0000-0002-8567-6020)
- Michael M. Allers (ORCID: https://orcid.org/0000-0003-3656-1064)
- Thuy Trinh (ORCID: https://orcid.org/0000-0002-8799-8760)
- Muzi Liu
- Jonathan M. Schneeweiss
Institutions
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Heidelberger Institut für Radioonkologie (DE)
- Immunité et Cancer (FR)
- National Center for Tumor Diseases (DE)
- Duke Medical Center (US)
- Translationale Onkologie an der Universitätsmedizin der Johannes Gutenberg-Universität Mainz (DE)
- DKFZ-ZMBH Alliance (DE)
Publication Details
- Journal
- JCI Insight
- Published
- 2025-08-14
- DOI
- https://doi.org/10.1172/jci.insight.190149
- Citations
- 1
- Primary Topic
- Radiation Therapy and Dosimetry
- Type
- article
- Field-Weighted Citation Impact
- 1.52
Funders
- AstraZeneca
- Deutsches Krebsforschungszentrum
- Accuray
- Deutsche Krebshilfe