A simulation study on the radiation-induced immune response of tumors after single fraction high-dose irradiation

Purpose: We investigated radiation-induced antitumor immunity and its suppression by hypoxia-inducible factor (HIF-1α) for radiosurgery (SRS) using an improved cellular automata (CA) model. Method: A two-dimensional Cellular Automata (CA) model was employed to simulate the impact of radiation on cancer cell death and subsequent immune responses. Cancer cells died from direct cell death from radiation and indirect cell death due to radiation-induced vascular damage. The model also incorporated radiation-induced immunity and immuno-suppression. It was incorporated into the model assuming that the death of cancer cells generates effector cells, forming complexes with cancer cells, and high radiation doses lead to vascular damage, inducing tumor hypoxia and increasing HIF-1α expression. The model was validated and subjected to sensitivity analysis by evaluating tumor volume changes post-irradiation and exploring the effects and sensitivity of radiation-induced immune responses. Results: The ratios of the tumor volume at 360 days post-irradiation and the SRS day (rTV) decreased with a higher P_ME, a higher P_comp, and a lower Th_HIF. The rTVs were 4.6 and 2.0 for P_ME = 0.1 and 0.9, 12.0 and 2.2 for P_comp = 0.1 and 0.9, and 1.5 and 15.3 for Th_HIF = 0.1 and 10.0, respectively. Conclusions: By modeling the activation and deactivation of the effectors, the improved CA model showed that the radiation-induced immunogenic cell death in the tumor caused a decrease in the post-irradiation volume by a factor of four for the therapeutic doses relative to non-immune reaction cases.