Center for Theoretical Biological Physics, Northeastern University, Boston, MA, 02115, USA.
Department of Physics, Northeastern University, Boston, MA, 02115, USA.
Bull Math Biol. 2023 Sep 1;85(10):93. doi: 10.1007/s11538-023-01201-z.
Tumors develop in a complex physical, biochemical, and cellular milieu, referred to as the tumor microenvironment. Of special interest is the set of immune cells that reciprocally interact with the tumor, the tumor-immune microenvironment (TIME). The diversity of cell types and cell-cell interactions in the TIME has led researchers to apply concepts from ecology to describe the dynamics. However, while tumor cells are known to induce immune cells to switch from anti-tumor to pro-tumor phenotypes, this type of ecological interaction has been largely overlooked. To address this gap in cancer modeling, we develop a minimal, ecological model of the TIME with immune cell conversion, to highlight this important interaction and explore its consequences. A key finding is that immune conversion increases the range of parameters supporting a co-existence phase in which the immune system and the tumor reach a stalemate. Our results suggest that further investigation of the consequences of immune cell conversion, using detailed, data-driven models, will be critical for greater understanding of TIME dynamics.
肿瘤在复杂的物理、生化和细胞环境中发展，这个环境被称为肿瘤微环境。特别值得关注的是一组与肿瘤相互作用的免疫细胞，即肿瘤免疫微环境（TIME）。TIME 中细胞类型的多样性和细胞间的相互作用促使研究人员应用生态学的概念来描述其动态。然而，尽管众所周知肿瘤细胞会诱导免疫细胞从抗肿瘤表型转变为促肿瘤表型，但这种生态相互作用在很大程度上被忽视了。为了解决癌症建模中的这一空白，我们开发了一个具有免疫细胞转换功能的 TIME 的最小生态模型，以突出这种重要的相互作用并探索其后果。一个关键的发现是，免疫转换增加了支持免疫系统和肿瘤达到僵持阶段的共存相的参数范围。我们的结果表明，使用详细的、数据驱动的模型进一步研究免疫细胞转换的后果，对于更好地理解 TIME 的动态将是至关重要的。
