Synergistic effects of combing proton- or X-irradiation with anti-PDL1 immunotherapy in two murine oral cancers

Background and purpose Combining radiation therapy with immunotherapy may be beneficial in treatment of head and neck cancer (HNC), but the combined effect may depend on tumor characteristics and the type of radiation. The purpose was to compare responses for two syngeneic tumor models in mice following X-ray or proton irradiation with or without immune checkpoint inhibition (ICI). Materials and methods MOC1 and MOC2 tumors were inoculated in the right hind leg of each mouse (C57BL/6J, n=159). Single-dose irradiation with X-rays or protons and administration of anti-PDL1 started when the tumors reached 200 mm3. Doses of 5-30 Gy were given. Time-dependent tumor volume data were analyzed with a regression model yielding the growth rate γ without irradiation and the reduction in growth rate per dose η. Relative biological effectiveness (RBE) was calculated as the ratio of η for X-rays to that of protons. Synergy between radiation and ICI was estimated as the ratio of η’s. Results MOC2 tumors grew faster and were more radioresistant than MOC1 tumors. ICI reduced the growth rate for MOC1 with 20±2% compared to controls, while no reduction was seen for MOC2. RBE for MOC1 wo/w ICI was 0.89±0.04 and 0.93±0.06, respectively, while it was 1.15±0.12 and 1.60±0.17, respectively, for MOC2. Combination synergy for X-rays was 1.22±0.08 and 0.96±0.11 in MOC1 and MOC2, respectively, while was it 1.27±0.06 and 1.33 ±0.13, respectively, for protons. Conclusions RBE for protons was dependent on use of ICI and tumor type. A greater synergy may be achieved when combining protons with ICI compared to X-rays and ICI. ### Competing Interest Statement The authors have declared no competing interest.