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Radiation-induced lymphopenia does not impact treatment efficacy in a mouse tumor model.
Telarovic, Irma; Yong, Carmen S M; Guckenberger, Matthias; Unkelbach, Jan; Pruschy, Martin.
Afiliación
  • Telarovic I; Laboratory for Applied Radiobiology, Dept. Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Yong CSM; Laboratory for Applied Radiobiology, Dept. Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Dept. Immunology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Guckenberger M; Dept. Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Unkelbach J; Dept. Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Pruschy M; Laboratory for Applied Radiobiology, Dept. Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. Electronic address: martin.pruschy@uzh.ch.
Neoplasia ; 31: 100812, 2022 09.
Article en En | MEDLINE | ID: mdl-35667149
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfopenia / Neoplasias Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Neoplasia Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfopenia / Neoplasias Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Neoplasia Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos