Exploring tumor-induced immunosuppression dynamics by myeloid-derived suppressor cells: insights via a fractional-order mathematical model

B. Krithika, P. Tamilalagan
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Abstract

This study investigates the intricate role of myeloid-derived suppressor cells (MDSCs) in inhibiting the immunological responses against malignancies by employing a delayed fractional-order mathematical model. The proposed mathematical model includes tumor cells, dendritic cells, macrophages, cytotoxic T lymphocytes (CTLs), and MDSCs as components of a five-dimensional deterministic system. Further, the model accounts for the duration of the mechanism by which MDSCs perform immunosuppressive activities. One such mechanism involves the release of immunosuppressive cytokines such as interleukin-10 (IL-10), and it is elucidated by incorporation of the time-delay parameter, \(\tau\). Basic properties of the system such as non-negativity and uniqueness of solutions as well as the existence of biologically feasible steady states are explored. The conditions for steady-state stability and existence of Hopf bifurcation concerning the delay parameter \((\tau )\) are established. We notice that the growth rate of cancer cells determines the stability nature of the tumor-free equilibrium, regardless of the time-delay \(\tau\). While the fractional-order \(\alpha\) does not affect the stability of steady states, however it does influence the transient behavior of the considered system.

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探索髓源性抑制细胞诱导的肿瘤免疫抑制动态:通过分数阶数学模型获得的启示
本研究采用延迟分数阶数学模型,研究了髓源性抑制细胞(MDSCs)在抑制针对恶性肿瘤的免疫反应中的复杂作用。提出的数学模型包括肿瘤细胞、树突状细胞、巨噬细胞、细胞毒性 T 淋巴细胞(CTL)和 MDSCs,它们是五维确定性系统的组成部分。此外,该模型还考虑了 MDSCs 执行免疫抑制活动的机制持续时间。这种机制之一涉及白细胞介素-10(IL-10)等免疫抑制细胞因子的释放,并通过加入时间延迟参数(time-delay parameter)加以阐明。研究探讨了系统的基本特性,如解的非负性和唯一性,以及生物可行稳态的存在。建立了关于延迟参数 \((\tau )\) 的稳态稳定和霍普夫分岔存在的条件。我们注意到,癌细胞的生长速度决定了无肿瘤平衡的稳定性,而与时间延迟无关。虽然分数阶不影响稳态的稳定性,但它会影响所考虑系统的瞬态行为。
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