Multi-scale modeling of macrophage—T cell interactions within the tumor microenvironment |
| |
| Authors: | Colin G. Cess Stacey D. Finley |
| |
| Affiliation: | 1. Department of Biomedical Engineering, University of Southern California, Los Angeles, California, United States of America;2. Department of Quantitative and Biological Sciences, University of Southern California, Los Angeles, California, United States of America;3. Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California, United States of America;Yale University, UNITED STATES |
| |
| Abstract: | Within the tumor microenvironment, macrophages exist in an immunosuppressive state, preventing T cells from eliminating the tumor. Due to this, research is focusing on immunotherapies that specifically target macrophages in order to reduce their immunosuppressive capabilities and promote T cell function. In this study, we develop an agent-based model consisting of the interactions between macrophages, T cells, and tumor cells to determine how the immune response changes due to three macrophage-based immunotherapeutic strategies: macrophage depletion, recruitment inhibition, and macrophage reeducation. We find that reeducation, which converts the macrophages into an immune-promoting phenotype, is the most effective strategy and that the macrophage recruitment rate and tumor proliferation rate (tumor-specific properties) have large impacts on therapy efficacy. We also employ a novel method of using a neural network to reduce the computational complexity of an intracellular signaling mechanistic model. |
| |
| Keywords: | |
|
|
