MicroMacro (2020-2024)
« MicroMacro : Did we underestimate, if not obscure, the inflammatory component and the role of TAMs in glial tumor response to synchrotron microbeam radiotherapy? »
In this project, we suggest to study the molecular mechanisms involved after microbeam radiation therapy (MRT, a method based on the spatial fractionation of microplanar synchrotron X-rays) of glial tumors. This unique geometry reduces significantly damages to the perilesional normal tissues while delivering very high doses (hectogray) to the tumors. This work aims at defining the effects and relevance of very high doses of radiation to tumor cells and to compare them with the effects of conventional radiotherapy (RT). We assume that the differential effect already demonstrated in vivo on vascular networks is also mediated at the molecular level. We will characterize the tumor tissue secretomes irradiated by MRT or RT using the Multiplex technology and we will identify cytokines / growth factors specifically involved in tumor response to MRT. Furthermore, we will demonstrate that the nature and effects of these secreted proteins are directly related to the phenotype of macrophages associated with brain tumors after MRT. Indeed, we hypothesize that very high doses of radiation deposited in the microbeam path promote contacts between cellular debris / tumor antigens which in turn polarize macrophages into the antitumoral M1 phenotype. Our preliminary results indicate that changes in the tumor microenvironment at the vascular, cellular and molecular scales allow the shift from M2 to M1 macrophages, and therefore the proteins they secrete; these changes result in an increased therapeutic efficacy of MRT compared with RT. The identification of such biological mechanisms specifically associated with MRT will explain the effectiveness of this new type of radiation therapy which has already appeared as a novel promising tool for cancer treatment.
Partners : ISTCT (Caen), INSERM UA07 (Grenoble), INSERM U1216 (Grenoble), INSERM 1205 (Grenoble), Équipe ProMD CEA (Grenoble)
Français (France) 
English (United Kingdom) 
