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

Abstract

Monocyte-derived macrophages are immune cells which help maintain tissue homeostasis and defend the organism against pathogens. In solid tumours, recent studies have uncovered complex macrophage populations, among which tumour-associated macrophages, supporting tumorigenesis through multiple cancer hallmarks such as immunosuppression, angiogenesis or matrix remodelling. In the case of chronic lymphocytic leukemia, these macrophages are known as nurse-like cells and have been shown to protect leukemic cells from spontaneous apoptosis and contribute to their chemoresistance. We propose an agent-based model of monocytes differentiation into nurse-like cells upon contact with leukemic B cells in-vitro. We studied monocyte differentiation and cancer cells survival dynamics depending on diverse hypotheses on monocytes and cancer cells relative proportions, sensitivity to their surrounding environment and cell-cell interactions. Peripheral blood mononuclear cells from patients were cultured and monitored during 13 days to calibrate the model parameters, such as phagocytosis efficiency, death rates or protective effect from the nurse-like cells. Our model is able to reproduce experimental results and predict cancer cells survival dynamics in a patient-specific manner. Our results shed light on important factors at play in cancer cells survival, highlighting a potentially important role of phagocytosis.