Mathematical modeling approach of cancer immunoediting reveals new insights in targeted-therapy and timing plan of cancer treatment

Abstract

Mathematical modeling was shown to be a powerful tool to describe immune system-cancer dynamics and specifically immunoediting. Here, we used a system of two ordinary differential equations to investigate the fate of the tumor through the three main phases of cancer immunoediting: elimination phase (elimination of cancer cells by the immune system), dormancy phase (equilibrium between tumor growth and immune system response), and escape phase (escape of cancer cells and growth of tumor). The role of the tumor growth rate, tumor immunogenic properties (immunogenicity or immunosuppressive effects), and tumor accessibility for the immune system were evaluated. The results show that decreasing the growth rate and increasing accessibility of the tumor for the immune system may help immunogenic tumors to survive elimination and become dormant; dormant tumors may wake up later on, causing tumor escape and growth. The model also indicated that the synchronization of immune response and tumor growth is a key factor for successful tumor elimination. Simulation results for the fate of the residual tumor cells after surgical tumor resection, revealed the importance of timing in adjuvant targeted-therapy: a too late or a too early start of targeted therapy may result in tumor escape or tumor dormancy, respectively, while start at an intermediate timing results in the elimination of the tumor. Results of this simulation are corroborated with experimental and clinical observations.