Proton FLASH Radiation Therapy and Immune Infiltration: Evaluation in an Orthotopic Glioma Rat Model.

Autor:	Iturri L; Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France. Electronic address: lorea.iturri@curie.fr., Bertho A; Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France., Lamirault C; Institut Curie, Université PSL, Département de Recherche Translationnelle, CurieCoreTech-Experimental Radiotherapy (RadeXp), Paris, France., Juchaux M; Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France., Gilbert C; Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France., Espenon J; Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France., Sebrie C; CEA, CNRS, Inserm, Service Hospitalier Frédéric Joliot, BIOMAPS Université Paris-Saclay, Orsay, France., Jourdain L; CEA, CNRS, Inserm, Service Hospitalier Frédéric Joliot, BIOMAPS Université Paris-Saclay, Orsay, France., Pouzoulet F; Institut Curie, Université PSL, Département de Recherche Translationnelle, CurieCoreTech-Experimental Radiotherapy (RadeXp), Paris, France., Verrelle P; Institut Curie, Campus Universitaire, PSL Research University, University Paris Saclay, INSERM LITO (U1288), Orsay, 91898 France; Centre de Protonthérapie d'Orsay, Radiation Oncology Department, Campus Universitaire, Institut Curie, PSL Research University, Orsay, 91898 France., De Marzi L; Institut Curie, Campus Universitaire, PSL Research University, University Paris Saclay, INSERM LITO (U1288), Orsay, 91898 France; Centre de Protonthérapie d'Orsay, Radiation Oncology Department, Campus Universitaire, Institut Curie, PSL Research University, Orsay, 91898 France., Prezado Y; Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France.
Jazyk:	angličtina
Zdroj:	International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] 2023 Jul 01; Vol. 116 (3), pp. 655-665. Date of Electronic Publication: 2022 Dec 21.
DOI:	10.1016/j.ijrobp.2022.12.018
Abstrakt:	Purpose: FLASH radiation therapy (FLASH-RT) is a promising radiation technique that uses ultrahigh doses of radiation to increase the therapeutic window of the treatment. FLASH-RT has been observed to provide normal tissue sparing at high dose rates and similar tumor control compared with conventional RT, yet the biological processes governing these radiobiological effects are still unknown. In this study, we sought to investigate the potential immune response generated by FLASH-RT in a high dose of proton therapy in an orthotopic glioma rat model. Methods and Materials: We cranially irradiated rats with a single high dose (25 Gy) using FLASH dose rate proton irradiation (257 ± 2 Gy/s) or conventional dose rate proton irradiation (4 ± 0.02 Gy/s). We first assessed the protective FLASH effect that resulted in our setup through behavioral studies in naïve rats. This was followed by a comprehensive analysis of immune cells in blood, healthy tissue of the brain, and tumor microenvironment by flow cytometry. Results: Proton FLASH-RT spared memory impairment produced by conventional high-dose proton therapy and induced a similar tumor infiltrating lymphocyte recruitment. Additionally, a general neuroinflammation that was similar in both dose rates was observed. Conclusions: Overall, this study demonstrated that FLASH proton therapy offers a neuro-protective effect even at high doses while mounting an effective lymphoid immune response in the tumor. (Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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