An agent-based model of monocyte differentiation into tumour-associated macrophages in chronic lymphocytic leukemia

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 (NLCs) and they protect leukemic cells from spontaneous apoptosis, contributing to their chemoresistance. We propose an agent-based model of monocyte differentiation into NLCs upon contact with leukemic B cells in vitro. We performed patient-specific model optimization using cultures of peripheral blood mononuclear cells from patients. Using our model, we were able to reproduce the 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 NLCs and in promoting cancer cells’ enhanced survival. [Display omitted] •Patient blood-derived cultures track tumor-associated macrophage formation in vitro•Agent-based model predicts macrophage polarization and cancer cell survival dynamics•Patient-specific models identify two groups with distinct macrophage phenotypes•Phagocytosis efficiencies and cancer cell heterogeneity drive the observed dynamics Health sciences; Immunology; Computational bioinformatics; Cancer