(329e) Modeling the Impact of Heterogeneity in the Early Tumor-Immune Response
Here, we investigate the effects of phenotypic differences among multiple cell types in the TME. We model cancer cells, macrophages, and T cells. Using an agent-based model, we simulate the interactions between these three cell types, along with several diffusible factors present in the TME. Importantly, we model the behavior of individual cells, to examine how differences at the cellular level compound into differences at the population level. In addition, to produce more physiologically relevant scenarios, we utilize mechanistic models of intracellular signaaling for some key pathways related to the immune response. The dynamics of these intracellular signaling responses determine how the cell will behave. Finally, we incorporate heterogeneity in three ways: allowing phenotypic parameters to vary between cells of the same type, varying the xpressions of proteins in the intracellular signaling networks from cell to cell, and varying the levels of extraceullar stimuli. With our model, we are able to examine the ffects of various types of heterogeneity on the initial immune response to cancer growth, with and without various macrophage-based treatment strategies. Altogether, we gain a better understanding of the complexities of the TME.