Novel insights in targeted therapy of cancer by mathematical modeling of cancer immunoediting

Computational modeling has advanced in recent decades and provides new opportunities for a betterunderstanding of immune system-cancer dynamics. Immunoediting is the process describing this dynamicand discusses immune system-cancer coevolution during tumorigenesis. It consists of three main phases;Elimination (elimination of cancer cells by the immune system), dormancy phase (balance between tumorgrowth and immune response), and escape (escape from immune response and growth of tumor). Here wemodeled the immunoediting, using a system of two ordinary differential equations to study the fate of thetumor through three main phases of cancer immunoediting. Using the model, we evaluated the role of thetumor growth rate, tumor immunogenic properties, and immune cells intratumoral penetration on the tumorfate through coevolution with the immune system. The results show that, interestingly, immunogenic tumorscan survive elimination and instead, become dormant by decreasing the growth rate and/or increasingaccessibility of the tumor for the immune system; Dormant tumors may wake up later on, causing tumorescape and growth. The model also indicated that the immune response and tumor growth synchronizationhas a significant role for tumor eradication. In other series of simulations, we evaluated the fate of the residualtumor cells after surgical tumor resection. The results revealed the importance of timing in adjuvant targetedtherapy of tumor residue: a too late or a too early start of targeted therapy may result in tumor escape ortumor dormancy, respectively, while starting at an intermediate timing results in the complete elimination ofthe tumor. Results of our model simulation are corroborated with experimental and clinical observations.

کلیدواژه ها:

Immunoediting ، Immune system-cancer synchronization ، Mathematical modeling ، Targeted therapy