Mathematical model of tumor-macrophage dynamics in glioma to advance myeloid-targeted therapies
Year: 2025
Type: article
Abstract: Recent biological research has highlighted the relevance of myeloid-cell populations in glioma growth, with a particular role played by tumor-associated macrophages (TAMs), which comprise resident microglia and monocyte-derived macrophages. Additionally, radiation therapy, the most common treatment for gliomas, significantly alters the tumor microenvironment, affecting TAMs and contributing to tumor recurrence. Promising preclinical studies have identified and developed drugs targeting TAMs. The development and combined deployment of these therapies require in silico techniques that enable us to optimize their outcomes. To do so, we need mathematical models of glioma growth and therapy response that explicitly incorporate TAMs-an often overlooked component in existing models. Here, we present a dynamical model of glioma growth driven by tumor-immune interactions. The model was parametrized using published data from mice experiments, including responses to ionizing radiation. We used this model to investigate glioma progression under radiotherapy combined with three treatments targeting distinct aspects of TAM biology. Simulations revealed that anti-CD47 enhanced the otherwise weak phagocytic activity, extending the upper tail of the survival curve. α-CD49d, which limits monocyte trafficking after irradiation, offered consistent survival benefits across digital twins of mice. Finally, CSF-1R inhibitors, which block the primary growth factor regulating TAM function, resulted in the largest overall survival improvement in silico. Our results aligned well with experimental evidence, suggesting that the model may help inform the optimization of myeloid cell-targeted immunotherapies, including their timing, dosage, and combination with radiation therapy, with potential relevance for improving glioma treatment strategies.
Authors: Jesús J. Bosque, Jordan Martínez, José García Otero, Guim Aguadé-Gorgorió, Javier E. Sanchez-Galan, Juan Belmonte-Beitia
Language: English
Subfield: Modeling and Simulation
Field: Mathematics
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,080
Funders: European Commission, Federación Española de Enfermedades Raras, Centre National de la Recherche Scientifique, Ministerio de Ciencia e Innovación, Conseil National de la Recherche Scientifique, Secretaria Nacional de Ciencia y Tecnología, Universidad de Castilla-La Mancha, Junta de Comunidades de Castilla-La Mancha, National Institutes of Health, European Regional Development Fund, Agencia Estatal de Investigación, Sistema Nacional de Investigadores, Sistema Nacional de Investigación, Secretaría Nacional de Ciencia, Tecnología e Innovación, National Cancer Institute, National Institute of Environmental Health Sciences, H2020 Marie Skłodowska-Curie Actions, HORIZON EUROPE Marie Sklodowska-Curie Actions
Awards: G164407118, G1855990336, G2262748287, G2309174360, G2601397997, G300979063, G3022634907, G3480869486, G3681454997, G3757545574, G4042783231, G410571670, G425668148, G430777504, G451917667, G4984348011, G5080475149, G5421974903, G5763709211, G5967599077, G5980429568, G6614993061, G7851645618, G7924217734, G8100984158, G8920660035, G8970673152, G9000273626, Radiation dosimetry for alpha-particle radiopharmaceutical therapy and application to pediatric neuroblastoma, G983164000
OpenAlex ID: W4413438458