1st International and 10th National Iranian Conference on Bioinformatics

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

Paper ID : 1130-ICB10

Authors:

Mojtaba Ghanizadeh *, Peyman Shariatpanahi, Bahram Goliaei

Biophysics Department, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

Abstract:

Computational modeling has advanced in recent decades and provides new opportunities for a better understanding of immune system-cancer dynamics[1]. Immunoediting is the process describing this dynamic and 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 tumor growth and immune response), and escape (escape from immune response and growth of tumor)[2]. Here we modeled the immunoediting, using a system of two ordinary differential equations to study the fate of the tumor through three main phases of cancer immunoediting. Using the model, we evaluated the role of the tumor growth rate, tumor immunogenic properties, and immune cells intratumoral penetration on the tumor fate through coevolution with the immune system. The results show that, interestingly, immunogenic tumors can survive elimination and instead, become dormant by decreasing the growth rate and/or increasing accessibility of the tumor for the immune system; Dormant tumors may wake up later on, causing tumor escape and growth. The model also indicated that the immune response and tumor growth synchronization has a significant role for tumor eradication. In other series of simulations, we evaluated the fate of the residual tumor cells after surgical tumor resection. The results revealed the importance of timing in adjuvant targeted therapy of tumor residue: a too late or a too early start of targeted therapy may result in tumor escape or tumor dormancy, respectively, while starting at an intermediate timing results in the complete elimination of the tumor. Results of our model simulation are corroborated with experimental and clinical observations.

Keywords:

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

Status : Paper Accepted (Oral Presentation)