多尺度移动边界肿瘤侵袭模型中巨噬细胞的再极化
Re-polarisation of macrophages within a multi-scale moving boundary tumour invasion model
摘要：
癌症对周围组织的侵袭是一个多尺度的过程，不仅涉及肿瘤细胞，还涉及环境中的其他免疫细胞，如肿瘤相关巨噬细胞（TAM）。这些免疫细胞的异质性，其中两个极端是促炎和抗肿瘤M1细胞，以及抗炎和促肿瘤M2细胞，对癌症侵袭具有显著影响，因为这些细胞以不同的方式与肿瘤细胞和细胞外基质（ECM）相互作用。实验研究表明，癌细胞与TAM共迁移，但这些不同的TAM亚群（可以改变其表型并根据微环境重新极化）对这种共迁移的影响尚未完全了解。在这项研究中，我们扩展了以前的多尺度移动边界数学模型，通过引入M1样巨噬细胞以及它们对肿瘤侵袭过程的多尺度影响。在这个模型的帮助下，我们在数值上研究了将M2 TAM重新极化为抗肿瘤M1表型的影响，以及这种策略如何影响整体肿瘤进展。特别是，我们研究了M2->M1复极化是否依赖于时间和/或空间，以及这种空间和时间依赖性复极化对肿瘤侵袭的宏观影响。
英文摘要：
Cancer invasion of the surrounding tissue is a multiscale process that involves not only tumour cells but also other immune cells in the environment, such as the tumour-associated macrophages (TAMs). The heterogeneity of these immune cells, with the two extremes being the pro-inflammatory and anti-tumour M1 cells, and the anti-inflammatory and pro-tumour M2 cells, has a significant impact on cancer invasion as these cell interact in different ways with the tumour cells and with the ExtraCellular Matrix (ECM). Experimental studies have shown that cancer cells co-migrate with TAMs, but the impact of these different TAM sub-populations (which can change their phenotype and re-polarise depending on the microenvironment) on this co-migration is not fully understood. In this study, we extend a previous multi-scale moving boundary mathematical model, by introducing the M1-like macrophages alongside with their exerted multi-scale effects on the tumour invasion process. With the help of this model we investigate numerically the impact of re-polarising the M2 TAMs into the anti-tumoral M1 phenotype and how such a strategy affects the overall tumour progression. In particular, we investigate numerically whether the M2-->M1 re-polarisation could depend on time and/or space, and what would be the macroscopic effects of this spatial- and temporal-dependent re-polarisation on tumour invasion.
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