Mohammad Mirzaei Navid, Hao Wenrui, Shahriyari Leili
Department of Mathematics and Statistics, University of Massachusetts Amherst, Amherst, 01003 MA, USA.
Department of Mathematics, Pennsylvania State University, University Park, 16802 PA, USA.
iScience. 2023 Apr 10;26(5):106596. doi: 10.1016/j.isci.2023.106596. eCollection 2023 May 19.
The intricate network of interactions between cells and molecules in the tumor microenvironment creates a heterogeneous ecosystem. The proximity of the cells and molecules to their activators and inhibitors is essential in the progression of tumors. Here, we develop a system of partial differential equations coupled with linear elasticity to investigate the effects of spatial interactions on the tumor microenvironment. We observe interesting cell and cytokine distribution patterns, which are heavily affected by macrophages. We also see that cytotoxic T cells get recruited and suppressed at the site of macrophages. Moreover, we observe that anti-tumor macrophages reorganize the patterns in favor of a more spatially restricted cancer and necrotic core. Furthermore, the adjoint-based sensitivity analysis indicates that the most sensitive model's parameters are directly related to macrophages. The results emphasize the widely acknowledged effect of macrophages in controlling cancer cells population and spatially arranging cells in the tumor microenvironment.
肿瘤微环境中细胞与分子之间复杂的相互作用网络形成了一个异质生态系统。细胞和分子与其激活剂和抑制剂的接近程度在肿瘤进展中至关重要。在此,我们开发了一个与线性弹性耦合的偏微分方程系统,以研究空间相互作用对肿瘤微环境的影响。我们观察到有趣的细胞和细胞因子分布模式,这些模式受到巨噬细胞的严重影响。我们还看到细胞毒性T细胞在巨噬细胞部位被募集和抑制。此外,我们观察到抗肿瘤巨噬细胞会重新组织这些模式,以利于形成空间上更受限的癌症和坏死核心。此外,基于伴随的敏感性分析表明,最敏感的模型参数与巨噬细胞直接相关。结果强调了巨噬细胞在控制癌细胞数量和在肿瘤微环境中对细胞进行空间排列方面广为人知的作用。