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bioRxiv · 10.1101/2021.12.17.473137

An Agent-Based Model of monocyte differentiation into Tumour-Associated Macrophages in Chronic Lymphocytic Leukemia

Verstraete, N.·Marku, M.·Domagala, M.·Bordenave, J.·Arduin, H.·FOURNIE, j. j.·Ysebaert, L.·Poupot, M.·Pancaldi, V.
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Abstract

Monocyte-derived macrophages help maintain tissue homeostasis and defend the organism against pathogens. In tumors, recent studies have uncovered complex macrophage populations, including tumor-associated macrophages, which support tumorigenesis through cancer hallmarks such as immunosuppression, angiogenesis or matrix remodeling. In the case of chronic lymphocytic leukemia, these macrophages are known as nurse-like cells and they protect leukemic cells from spontaneous apoptosis contributing to their chemoresistance. We propose an agent-based model of monocyte differentiation into nurse-like cells upon contact with leukemic B cells in vitro. We performed patient-specific model calibrations using cultures of peripheral blood mononuclear cells from patients. Using our model, we were able to reproduce temporal survival dynamics of cancer cells in a patient-specific manner and to identify patient groups related to distinct macrophage phenotypes. Our results show a potentially important role of phagocytosis in the polarization process of nurse-like cells and in promoting cancer cells enhanced survival.

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Verstraete, N., Marku, M., Domagala, M., Bordenave, J., Arduin, H., FOURNIE, j. j., Ysebaert, L., Poupot, M., Pancaldi, V.. 2021-12-20. An Agent-Based Model of monocyte differentiation into Tumour-Associated Macrophages in Chronic Lymphocytic Leukemia. https://doi.org/10.1101/2021.12.17.473137

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