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肿瘤免疫监视的数学模型

Mathematical model of tumor-immune surveillance.

作者信息

Mahasa Khaphetsi Joseph, Ouifki Rachid, Eladdadi Amina, Pillis Lisette de

机构信息

DST/NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), University of Stellenbosch, Stellenbosch, South Africa.

DST/NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), University of Stellenbosch, Stellenbosch, South Africa.

出版信息

J Theor Biol. 2016 Sep 7;404:312-330. doi: 10.1016/j.jtbi.2016.06.012. Epub 2016 Jun 16.

Abstract

We present a novel mathematical model involving various immune cell populations and tumor cell populations. The model describes how tumor cells evolve and survive the brief encounter with the immune system mediated by natural killer (NK) cells and the activated CD8(+) cytotoxic T lymphocytes (CTLs). The model is composed of ordinary differential equations describing the interactions between these important immune lymphocytes and various tumor cell populations. Based on up-to-date knowledge of immune evasion and rational considerations, the model is designed to illustrate how tumors evade both arms of host immunity (i.e. innate and adaptive immunity). The model predicts that (a) an influx of an external source of NK cells might play a crucial role in enhancing NK-cell immune surveillance; (b) the host immune system alone is not fully effective against progression of tumor cells; (c) the development of immunoresistance by tumor cells is inevitable in tumor immune surveillance. Our model also supports the importance of infiltrating NK cells in tumor immune surveillance, which can be enhanced by NK cell-based immunotherapeutic approaches.

摘要

我们提出了一种涉及多种免疫细胞群体和肿瘤细胞群体的新型数学模型。该模型描述了肿瘤细胞如何在自然杀伤(NK)细胞和活化的CD8(+)细胞毒性T淋巴细胞(CTL)介导的与免疫系统的短暂接触中进化并存活。该模型由常微分方程组成,描述了这些重要免疫淋巴细胞与各种肿瘤细胞群体之间的相互作用。基于最新的免疫逃逸知识和合理考量,该模型旨在阐明肿瘤如何逃避宿主免疫的两个分支(即先天免疫和适应性免疫)。该模型预测:(a)外部NK细胞源的流入可能在增强NK细胞免疫监视中起关键作用;(b)仅宿主免疫系统对肿瘤细胞的进展并不完全有效;(c)在肿瘤免疫监视中,肿瘤细胞产生免疫抗性是不可避免的。我们的模型还支持浸润性NK细胞在肿瘤免疫监视中的重要性,基于NK细胞的免疫治疗方法可增强这种重要性。

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