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肿瘤逃避免疫系统控制的简单生物物理模型。

Simple biophysical model of tumor evasion from immune system control.

作者信息

d'Onofrio Alberto, Ciancio Armando

机构信息

European Institute of Oncology, Department of Experimental Oncology, Via Ripamonti 435, I-20141 Milano, Italy.

出版信息

Phys Rev E Stat Nonlin Soft Matter Phys. 2011 Sep;84(3 Pt 1):031910. doi: 10.1103/PhysRevE.84.031910. Epub 2011 Sep 12.

Abstract

The competitive nonlinear interplay between a tumor and the host's immune system is not only very complex but is also time-changing. A fundamental aspect of this issue is the ability of the tumor to slowly carry out processes that gradually allow it to become less harmed and less susceptible to recognition by the immune system effectors. Here we propose a simple epigenetic escape mechanism that adaptively depends on the interactions per time unit between cells of the two systems. From a biological point of view, our model is based on the concept that a tumor cell that has survived an encounter with a cytotoxic T-lymphocyte (CTL) has an information gain that it transmits to the other cells of the neoplasm. The consequence of this information increase is a decrease in both the probabilities of being killed and of being recognized by a CTL. We show that the mathematical model of this mechanism is formally equal to an evolutionary imitation game dynamics. Numerical simulations of transitory phases complement the theoretical analysis. Implications of the interplay between the above mechanisms and the delivery of immunotherapies are also illustrated.

摘要

肿瘤与宿主免疫系统之间竞争性的非线性相互作用不仅非常复杂,而且随时间变化。这个问题的一个基本方面是肿瘤缓慢进行一些过程的能力,这些过程逐渐使其受到的伤害减少,对免疫系统效应器的识别也不那么敏感。在此,我们提出一种简单的表观遗传逃逸机制,它自适应地依赖于两个系统细胞之间每单位时间的相互作用。从生物学角度来看,我们的模型基于这样一个概念,即与细胞毒性T淋巴细胞(CTL)相遇后存活下来的肿瘤细胞会获得信息,并将其传递给肿瘤的其他细胞。这种信息增加的结果是被CTL杀死和识别的概率都降低。我们表明,该机制的数学模型在形式上等同于进化模仿博弈动力学。过渡阶段的数值模拟补充了理论分析。还说明了上述机制与免疫治疗递送之间相互作用的影响。

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