Radiation-induced lymphopenia does not impact treatment efficacy in a mouse tumor model
Radiation-induced lymphopenia is a common occurrence in radiation oncology and an established negative prognostic factor, however the mechanisms underlying the relationship between lymphopenia and inferior survival remain elusive. The relevance of lymphocyte co-irradiation as critical normal tissue...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558622000392 |
| _version_ | 1811289410478538752 |
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| author | Irma Telarovic Carmen S.M. Yong Matthias Guckenberger Jan Unkelbach Martin Pruschy |
| author_facet | Irma Telarovic Carmen S.M. Yong Matthias Guckenberger Jan Unkelbach Martin Pruschy |
| author_sort | Irma Telarovic |
| collection | DOAJ |
| description | Radiation-induced lymphopenia is a common occurrence in radiation oncology and an established negative prognostic factor, however the mechanisms underlying the relationship between lymphopenia and inferior survival remain elusive. The relevance of lymphocyte co-irradiation as critical normal tissue component at risk is an emerging topic of high clinical relevance, even more so in the context of potentially synergistic radiotherapy-immunotherapy combinations.The impact of the radiotherapy treatment volume on the lymphocytes of healthy and tumor-bearing mice was investigated in a novel mouse model of radiation-induced lymphopenia. Using an image-guided small-animal radiotherapy treatment platform, translationally relevant tumor-oriented volumes of irradiation with an anatomically defined increasing amount of normal tissue were irradiated, with a focus on the circulating blood and lymph nodes. In healthy mice, the influence of irradiation with increasing radiotherapy treatment volumes was quantified on the level of circulating blood cells and in the spleen. A significant decrease in the lymphocytes was observed in response to irradiation, including the minimally irradiated putative tumor area. The extent of lymphopenia correlated with the increasing volumes of irradiation. In tumor-bearing mice, differential radiotherapy treatment volumes did not influence the overall therapeutic response to radiotherapy alone. Intriguingly, an improved treatment efficacy in mice treated with draining-lymph node co-irradiation was observed in combination with an immune checkpoint inhibitor.Taken together, our study reveals compelling data on the importance of radiotherapy treatment volume in the context of lymphocytes as critical components of normal tissue co-irradiation and highlights emerging challenges at the interface of radiotherapy and immunotherapy. |
| first_indexed | 2024-04-13T03:54:03Z |
| format | Article |
| id | doaj.art-45a00ca86aff4c10895a3a5e62df16c8 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-04-13T03:54:03Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-45a00ca86aff4c10895a3a5e62df16c82022-12-22T03:03:42ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862022-09-0131100812Radiation-induced lymphopenia does not impact treatment efficacy in a mouse tumor modelIrma Telarovic0Carmen S.M. Yong1Matthias Guckenberger2Jan Unkelbach3Martin Pruschy4Laboratory for Applied Radiobiology, Dept. Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, SwitzerlandLaboratory for Applied Radiobiology, Dept. Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Dept. Immunology, University Hospital Zurich, University of Zurich, Zurich, SwitzerlandDept. Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, SwitzerlandDept. Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, SwitzerlandLaboratory for Applied Radiobiology, Dept. Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Corresponding author at: Dept. Radiation Oncology, University Hospital Zurich, Winterthurerstr. 190, CH-8057 Zurich, Switzerland.Radiation-induced lymphopenia is a common occurrence in radiation oncology and an established negative prognostic factor, however the mechanisms underlying the relationship between lymphopenia and inferior survival remain elusive. The relevance of lymphocyte co-irradiation as critical normal tissue component at risk is an emerging topic of high clinical relevance, even more so in the context of potentially synergistic radiotherapy-immunotherapy combinations.The impact of the radiotherapy treatment volume on the lymphocytes of healthy and tumor-bearing mice was investigated in a novel mouse model of radiation-induced lymphopenia. Using an image-guided small-animal radiotherapy treatment platform, translationally relevant tumor-oriented volumes of irradiation with an anatomically defined increasing amount of normal tissue were irradiated, with a focus on the circulating blood and lymph nodes. In healthy mice, the influence of irradiation with increasing radiotherapy treatment volumes was quantified on the level of circulating blood cells and in the spleen. A significant decrease in the lymphocytes was observed in response to irradiation, including the minimally irradiated putative tumor area. The extent of lymphopenia correlated with the increasing volumes of irradiation. In tumor-bearing mice, differential radiotherapy treatment volumes did not influence the overall therapeutic response to radiotherapy alone. Intriguingly, an improved treatment efficacy in mice treated with draining-lymph node co-irradiation was observed in combination with an immune checkpoint inhibitor.Taken together, our study reveals compelling data on the importance of radiotherapy treatment volume in the context of lymphocytes as critical components of normal tissue co-irradiation and highlights emerging challenges at the interface of radiotherapy and immunotherapy.http://www.sciencedirect.com/science/article/pii/S1476558622000392RadiotherapyNormal tissue injuryLymphopeniaImage-guided small animal radiotherapy platformRadioimmunotherapy |
| spellingShingle | Irma Telarovic Carmen S.M. Yong Matthias Guckenberger Jan Unkelbach Martin Pruschy Radiation-induced lymphopenia does not impact treatment efficacy in a mouse tumor model Neoplasia: An International Journal for Oncology Research Radiotherapy Normal tissue injury Lymphopenia Image-guided small animal radiotherapy platform Radioimmunotherapy |
| title | Radiation-induced lymphopenia does not impact treatment efficacy in a mouse tumor model |
| title_full | Radiation-induced lymphopenia does not impact treatment efficacy in a mouse tumor model |
| title_fullStr | Radiation-induced lymphopenia does not impact treatment efficacy in a mouse tumor model |
| title_full_unstemmed | Radiation-induced lymphopenia does not impact treatment efficacy in a mouse tumor model |
| title_short | Radiation-induced lymphopenia does not impact treatment efficacy in a mouse tumor model |
| title_sort | radiation induced lymphopenia does not impact treatment efficacy in a mouse tumor model |
| topic | Radiotherapy Normal tissue injury Lymphopenia Image-guided small animal radiotherapy platform Radioimmunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S1476558622000392 |
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