Although conventional radiotherapy based on X-rays improves brain tumour patient survival, it also leads to deleterious effects on the inflammatory component: enrichment of pro-tumour macrophages1 as well as recruitment of myeloid cells at the tumour site and severe lymphopenia2. This radiation-induced lymphopenia and enrichment in protumoral macrophages in the tumour bulk could decrease the immunotherapeutic response and are associated to a poor prognosis3. Proton therapy has emerged as a new radiation strategy for brain tumours. Thanks to its precise dose deposition, it enables to spare healthy tissue and circulating leukocytes4, and to its different biological effects on the irradiated tissue5, it could result in less harmful effects for systemic inflammation6. In this project, we aim to evaluate if brain radiation with proton therapy is less deleterious for circulating leukocytes than conventional brain radiotherapy. Tumour-free mice have been irradiated with X-rays (X-Rad 225 Cx GIP CYCERON, Caen) or proton beams (25MeV PRECy platform, Strasbourg). For each type of radiation, mice were divided according to radiation volume (whole-brain or hemisphere). Mice were irradiated twice a day (2.5 Gy/session) for four consecutive days. Blood samples were collected before, during and after radiation and circulating leukocytes were analysed by flow cytometry. First experiments confirmed the feasibility of the protocol. Preliminary data showed that mice weight decreased after whole-brain radiation with X-rays but not with proton beams. Blood sampling confirmed radiation-induced lymphopenia after irradiation with X-Rays, wholebrain irradiation inducing a more pronounced effect than hemisphere irradiation. Changes in leukocytes after proton-irradiation are under investigation but preliminary results suggest a conservative effect on leukocytes. Proton therapy appears as a better radiotherapy option for brain tumour but its effects on inflammation remains to be further analysed.