A biomathematical model of tumor response to radioimmunotherapy with $α$PDL1 and $α$CTLA4

Abstract

There is evidence of synergy between radiotherapy and immunotherapy. Radiotherapy can increase liberation of tumor antigens, leading to activation of antitumor T-cells. This effect can be boosted with immunotherapy. Radioimmunotherapy is therefore a very promising therapeutic combination against cancer, with potential to increase tumor control rates. Biomathematical response models of radioimmunotherapy may help clinicians to design optimal treatment schedules. In this work we present a biomathematical model of tumor response to radioimmunotherapy. The model uses the linear-quadratic response of tumor cells to radiation, and builds on previous developments to include the radiation-induced immune effect. We have focused this study on the combined effect of radiotherapy and αPDL1/αCTL4 therapies. The model fits recent preclinical data of volume dynamics and control obtained with different dose fractionations and αPDL1/αCTL4. A biomathematical study of optimal combination strategies suggests that a good understanding of the biological delays associated to radoimmunotherapy, the biokinetics of the immunotherapy drug, and the interplay among them, may be of paramount importance to design optimal radioimmunotherapy schedules. Biomathematical models like the one we present can help to interpret experimental data on the synergy between radiotherapy and immunotherapy, and to assist in the design of more effective treatments, could potentially boost the implementation of radioimmunotherapy.