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Peer-reviewedCC BY 4.0NPJ Precision Oncology

Dynamic alterations in the irradiated draining lymph node

  • Sabrina Reichl1,2
  • Lisa Kurz3
  • Alba Sanchez Fernandez1
  • Elina Bugar3
  • Irene Vetrugno1
  • Burkhard Ludewig3
  • Martin Pruschy1
  • Irma Telarovic1,2
  1. 1Laboratory for Applied Radiobiology, University of Zurich, Zurich, Switzerland
  2. 2Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland
  3. 3Institute of Immunobiology, Medical Research Center, Cantonal Hospital St.Gallen, St. Gallen, Switzerland
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Abstract

Tumor-draining lymph nodes (DLNs) are crucial for the development of anti-tumor immunity upon irradiation. However, in radiotherapy, DLNs are frequently co-irradiated, which impairs their function. Here, we examine the consequences of DLN irradiation on anti-tumor immunity, focusing on the recently described radiotherapy-induced disruption of the CCR7-CCL19/CCL21 axis, which governs tumor-to-DLN trafficking. We use in vivo irradiated murine LNs and in vitro assays to assess irradiation-induced structural and functional changes in the DLNs. DLN-infiltrating lymphocytes and CCL19/CCL21 chemokines were depleted early after irradiation in a dose-dependent manner. Lymphocyte numbers recovered only in DLNs irradiated with 5 Gy or less. Lymphopenia persisted in DLNs irradiated with 15 Gy, with few surviving lymphocytes showing a compensatory increase in proliferation. Irradiation-deregulated secretion of CCL19 could be related to lymphodepletion and/or direct irradiation-induced processes in stromal cells. In conclusion, radiotherapy depletes DLNs, and impairs stromal function and chemokine signaling, thereby compromising anti-tumor immunity.

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Cite

BibTeXRIS
BibTeX
@article{reichl2026dynamic,
  title = {{Dynamic alterations in the irradiated draining lymph node}},
  author = {Sabrina Reichl and Lisa Kurz and Alba Sanchez Fernandez and Elina Bugar and Irene Vetrugno and Burkhard Ludewig and Martin Pruschy and Irma Telarovic},
  journal = {NPJ Precision Oncology},
  year = {2026},
  month = jul,
  doi = {10.1038/s41698-026-01610-y},
  url = {https://doi.org/10.1038/s41698-026-01610-y},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Dynamic alterations in the irradiated draining lymph node
AU  - Sabrina Reichl
AU  - Lisa Kurz
AU  - Alba Sanchez Fernandez
AU  - Elina Bugar
AU  - Irene Vetrugno
AU  - Burkhard Ludewig
AU  - Martin Pruschy
AU  - Irma Telarovic
PY  - 2026
DA  - 2026/07/11
JO  - NPJ Precision Oncology
DO  - 10.1038/s41698-026-01610-y
UR  - https://doi.org/10.1038/s41698-026-01610-y
AB  - Tumor-draining lymph nodes (DLNs) are crucial for the development of anti-tumor immunity upon irradiation. However, in radiotherapy, DLNs are frequently co-irradiated, which impairs their function. Here, we examine the consequences of DLN irradiation on anti-tumor immunity, focusing on the recently described radiotherapy-induced disruption of the CCR7-CCL19/CCL21 axis, which governs tumor-to-DLN trafficking. We use in vivo irradiated murine LNs and in vitro assays to assess irradiation-induced structural and functional changes in the DLNs. DLN-infiltrating lymphocytes and CCL19/CCL21 chemokines were depleted early after irradiation in a dose-dependent manner. Lymphocyte numbers recovered only in DLNs irradiated with 5 Gy or less. Lymphopenia persisted in DLNs irradiated with 15 Gy, with few surviving lymphocytes showing a compensatory increase in proliferation. Irradiation-deregulated secretion of CCL19 could be related to lymphodepletion and/or direct irradiation-induced processes in stromal cells. In conclusion, radiotherapy depletes DLNs, and impairs stromal function and chemokine signaling, thereby compromising anti-tumor immunity.
SN  - 2397-768X
ER  -