Synergistic Effect of Immunotherapy and Radiotherapy: a Computational Model

The Nobel Prize in Medicine 2018 was awarded for discovery of cancer immunotherapy (IT). Treatment effects are impressive, however, only a minority of patients respond. Because of favourable effects of radiotherapy (RT) on the immune system, combinations of IT and RT have been widely studied to improve the response rates. To identify possible biomarkers of response, we built a physical model capable of simulating tumour response to IT + RT. Interplay between a tumour, the immune system and the therapeutic effects is described with an experimentally verifiable population model, because the underlying biology is described with a minimum number of parameters. The model was able to reproduce experimental results from literature. To analyse possible biomarkers of response, sensitivity study of key parameters was performed. The most sensitive parameter was major histocompatibility complex class I expression, i.e. a receptor responsible for presentation of foreign proteins. Model predictions will be benchmarked against experiments on 3 different murine tumours, which will receive a single dose of RT with different IT schedules. Such models show promise to support, guide and accelerate immunotherapy research.