Agent-based Modeling of Tumor and Immune System Interactions in Combinational Therapy with Low-dose 5-fluorouracil and Dendritic Cell Vaccine in Melanoma B16F10.

This study is designed to present an agent-based model (ABM) to simulate the interactions between tumor cells and the immune system in the melanoma model. The Myeloid-derived Suppressor Cells (MDSCs) and dendritic cells (DCs) are considered in this model as immunosuppressive and antigen-presenting agents respectively. The animal experiment was performed on 68 B16F10 melanoma tumor-bearing C57BL/6 female mice to collect dynamic data for ABM implementation and validation. Animals were divided into 4 groups; group 1 was control (no treatment) while groups 2 and 3 were treated with DC vaccine and low-dose 5- fluorouracil (5-FU) respectively and group 4 was treated with both DC Vaccine and low-dose of 5-FU. The tumor growth rate, number of MDSC, and presence of CD8+/CD107a+ T cells in the tumor microenvironment were evaluated in each group. Firstly, the tumor cells, the effector immune cells, DCs, and the MDSCs have been considered as the agents of the ABM model and their interaction methods have been extracted from the literature and implemented in the model. Then, the model parameters were estimated by the dynamic data collected from animal experiments.  To validate the ABM model, the simulation results were compared with the real data. The results show that the dynamics of the model agents can mimic the relations among considered immune system components to an emergent outcome compatible with real data. The simplicity of the proposed model can help to understand the results of the combinational therapy and make this model a useful tool for studying different scenarios and assessing the combinational results. Determining the role of each component helps to find critical times during tumor progression and change the tumor and immune system balance in favor of the immune system.