Multi-scale modeling of macrophage-T cell interactions within the tumor microenvironment.
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 func...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-12-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1008519 |
| Summary: | 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. |
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| ISSN: | 1553-734X 1553-7358 |