Oxygen supplementation in anesthesia can block FLASH effect and anti-tumor immunity in conventional proton therapy.

Autor: Iturri L; Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France.; Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France., Bertho A; Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France.; Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France., Lamirault C; Translational Research Department, Institut Curie, Experimental Radiotherapy Platform, Université Paris Saclay, Orsay, France., Brisebard E; INRAE Oniris, UMR703 PAnTher - APEX, Nantes, France., Juchaux M; Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France.; Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France., Gilbert C; Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France.; Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France., Espenon J; Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France.; Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France., Sébrié C; Service Hospitalier Frederic Joliot, CEA, CNRS, Inserm, BIOMAPS Universite Paris-Saclay, Orsay, France., Jourdain L; Service Hospitalier Frederic Joliot, CEA, CNRS, Inserm, BIOMAPS Universite Paris-Saclay, Orsay, France., de Marzi L; Institut Curie, Université PSL, Université Paris-Saclay, Inserm U1288, Laboratoire de Recherche Translationnelle en Oncologie (LITO), Orsay, France.; Institut Curie, Radiation Oncology Department, Campus universitaire, Orsay, France., Pouzoulet F; Translational Research Department, Institut Curie, Experimental Radiotherapy Platform, Université Paris Saclay, Orsay, France.; Institut Curie, Université PSL, Université Paris-Saclay, Inserm U1288, Laboratoire de Recherche Translationnelle en Oncologie (LITO), Orsay, France., Muret J; Institut Curie, Université PSL, Department of Anesthesia and Intensive Care, Paris, France., Verrelle P; Institut Curie, Radiation Oncology Department, Campus universitaire, Orsay, France.; Institut Curie, Université Paris-Saclay, Inserm U1196, CNRS UMR9187, Chimie et Modélisation pour la Biologie du Cancer (CMBC), Orsay, France., Prezado Y; Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France. yolanda.prezado@curie.fr.; Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France. yolanda.prezado@curie.fr.
Jazyk: angličtina
Zdroj: Communications medicine [Commun Med (Lond)] 2023 Dec 15; Vol. 3 (1), pp. 183. Date of Electronic Publication: 2023 Dec 15.
DOI: 10.1038/s43856-023-00411-9
Abstrakt: Background: Radiation-induced neurocognitive dysfunction is a major adverse effect of brain radiation therapy and has specific relevance in pediatric oncology, where serious cognitive deficits have been reported in survivors of pediatric brain tumors. Moreover, many pediatric patients receive proton therapy under general anesthesia or sedation to guarantee precise ballistics with a high oxygen content for safety. The present study addresses the relevant question of the potential effect of supplemental oxygen administered during anesthesia on normal tissue toxicity and investigates the anti-tumor immune response generated following conventional and FLASH proton therapy.
Methods: Rats (Fischer 344) were cranially irradiated with a single high dose of proton therapy (15 Gy or 25 Gy) using FLASH dose rate proton irradiation (257 ± 2 Gy/s) or conventional dose rate proton irradiation (4 ± 0.02 Gy/s), and the toxicities in the normal tissue were examined by histological, cytometric and behavioral analysis. Glioblastoma-bearing rats were irradiated in the same manner and tumor-infiltrating leukocytes were quantified by flow cytometry.
Results: Our findings indicate that supplemental oxygen has an adverse impact on both functional and anatomical evaluations of normal brain following conventional and FLASH proton therapy. In addition, oxygen supplementation in anesthesia is particularly detrimental for anti-tumor immune response by preventing a strong immune cell infiltration into tumoral tissues following conventional proton therapy.
Conclusions: These results demonstrate the need to further optimize anesthesia protocols used in radiotherapy with the goal of preserving normal tissues and achieving tumor control, specifically in combination with immunotherapy agents.
(© 2023. The Author(s).)
Databáze: MEDLINE
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