Verstraete Nina, Marku Malvina, Domagala Marcin, Arduin Hélène, Bordenave Julie, Fournié Jean-Jacques, Ysebaert Loïc, Poupot Mary, Pancaldi Vera
CRCT, Université de Toulouse, Inserm, CNRS, Université Toulouse III-Paul Sabatier, Centre de Recherches en Cancérologie de Toulouse, Toulouse, France.
Service d'Hématologie, Institut Universitaire du Cancer de Toulouse-Oncopole, 31330 Toulouse, France.
iScience. 2023 May 19;26(6):106897. doi: 10.1016/j.isci.2023.106897. eCollection 2023 Jun 16.
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 . 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.
单核细胞衍生的巨噬细胞有助于维持组织稳态，并保护机体抵御病原体。在肿瘤中，最近的研究发现了复杂的巨噬细胞群体，包括肿瘤相关巨噬细胞，它们通过免疫抑制、血管生成或基质重塑等癌症特征来支持肿瘤发生。在慢性淋巴细胞白血病中，这些巨噬细胞被称为类护士细胞（NLCs），它们保护白血病细胞免于自发凋亡，从而导致其化疗耐药性。我们提出了一种基于主体的模型，用于描述单核细胞在与白血病B细胞接触后分化为NLCs的过程。我们使用患者外周血单核细胞培养物进行了患者特异性模型优化。利用我们的模型，我们能够以患者特异性的方式重现癌细胞的时间存活动态，并识别与不同巨噬细胞表型相关的患者群体。我们的结果表明，吞噬作用在NLCs的极化过程以及促进癌细胞增强存活方面可能具有重要作用。
