Article ID Journal Published Year Pages File Type
4496398 Journal of Theoretical Biology 2013 12 Pages PDF
Abstract

•PDE model of tumor growth.•Tumor associated macrophages.•The transition from M1 to M2 macrophages under influence of the cancer.•Role of CD200R in immunoediting.•IL-10 downregulation in M2 and IL-12 upregulation in M1.

CD200 is a cell membrane protein that interacts with CD200 receptor (CD200R) of myeloid lineage cells. During tumor initiation and progression, CD200-positive tumor cells can interact with M1 and M2 macrophages through CD200–CD200R-compex, and downregulate IL-10 and IL-12 productions secreted primarily by M2 and M1 macrophages, respectively. In the tumor microenvironment, IL-10 inhibits the activation of cytotoxic T lymphocytes (CTL), while IL-12 enhances CTL activation. In this paper, we used a system approach to determine the combined effect of CD200–CD200R interaction on tumor proliferation by developing a mathematical model. We demonstrate that blocking CD200 on tumor cells may have opposite effects on tumor proliferation depending on the “affinity” of the macrophages to form the CD200–CD200R-complex with tumor cells. Our results help understanding the complexities of tumor microenvironment.

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