Computational Modeling of the Crosstalk Between Macrophage Polarization and Tumor Cell Plasticity in the Tumor Microenvironment

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dc.citation.journalTitleFrontiers in Oncologyen_US
dc.contributor.authorLi, Xuefeien_US
dc.contributor.authorJolly, Mohit Kumaren_US
dc.contributor.authorGeorge, Jason T.en_US
dc.contributor.authorPienta, Kenneth J.en_US
dc.contributor.authorLevine, Herberten_US
dc.date.accessioned2019-12-06T15:32:27Zen_US
dc.date.available2019-12-06T15:32:27Zen_US
dc.date.issued2019en_US
dc.description.abstractTumor microenvironments contain multiple cell types interacting among one another via different signaling pathways. Furthermore, both cancer cells and different immune cells can display phenotypic plasticity in response to these communicating signals, thereby leading to complex spatiotemporal patterns that can impact therapeutic response. Here, we investigate the crosstalk between cancer cells and macrophages in a tumor microenvironment through in silico (computational) co-culture models. In particular, we investigate how macrophages of different polarization (M1 vs. M2) can interact with epithelial-mesenchymal plasticity of cancer cells, and conversely, how cancer cells exhibiting different phenotypes (epithelial vs. mesenchymal) can influence the polarization of macrophages. Based on interactions documented in the literature, an interaction network of cancer cells and macrophages is constructed. The steady states of the network are then analyzed. Various interactions were removed or added into the constructed-network to test the functions of those interactions. Also, parameters in the mathematical models were varied to explore their effects on the steady states of the network. In general, the interactions between cancer cells and macrophages can give rise to multiple stable steady-states for a given set of parameters and each steady state is stable against perturbations. Importantly, we show that the system can often reach one type of stable steady states where cancer cells go extinct. Our results may help inform efficient therapeutic strategies.en_US
dc.identifier.citationLi, Xuefei, Jolly, Mohit Kumar, George, Jason T., et al.. "Computational Modeling of the Crosstalk Between Macrophage Polarization and Tumor Cell Plasticity in the Tumor Microenvironment." <i>Frontiers in Oncology,</i> (2019) Frontiers: https://doi.org/10.3389/fonc.2019.00010.en_US
dc.identifier.digitalfonc-09-00010en_US
dc.identifier.doihttps://doi.org/10.3389/fonc.2019.00010en_US
dc.identifier.urihttps://hdl.handle.net/1911/107800en_US
dc.language.isoengen_US
dc.publisherFrontiersen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleComputational Modeling of the Crosstalk Between Macrophage Polarization and Tumor Cell Plasticity in the Tumor Microenvironmenten_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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