Impact of proton therapy on antitumor immune response

Abstract Radiotherapy delivered using photons induces an immune response that leads to modulation of the tumor microenvironment. Clinical studies are ongoing to evaluate immune checkpoint inhibitors in association with photon radiotherapy. At present, there is no publication on the radio-induced immune response after proton therapy. Balb/c mice bearing subcutaneous CT26 colon tumors were irradiated by a single fraction of 16.4 Gy using a proton beam extracted from a TR24 cyclotron. RNA sequencing analysis was assessed at 3 days post-treatment. Proton therapy immune response was monitored by flow cytometry using several panels (lymphoid, myeloid cells, lymphoid cytokines) at 7 and 14 days post-irradiation. RNA-Seq functional profiling identified a large number of GO categories linked to “immune system” and “interferon signaling”. Immunomonitoring evaluation showed induced tumor infiltration by immune cells. This is the first study showing the effect of proton therapy on immune response. These interesting results provide a sound basis to assess the efficacy of a combination of proton therapy and immune checkpoint inhibitors.