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具有内在招募延迟和化疗的竞争肿瘤免疫系统中的稳定性和 Hopf 分支

Stability and Hopf bifurcations in a competitive tumour-immune system with intrinsic recruitment delay and chemotherapy.

机构信息

School of Mathematics and Statistics, Southwest University, Chongqing 400715, China.

出版信息

Math Biosci Eng. 2021 Feb 24;18(3):1941-1965. doi: 10.3934/mbe.2021101.

Abstract

In this paper, a three-dimensional nonlinear delay differential system including Tumour cells, cytotoxic-T lymphocytes, T-helper cells is constructed to investigate the effects of intrinsic recruitment delay and chemotherapy. It is found that the introduction of chemotherapy and time delay can generate richer dynamics in tumor-immune system. In particular, there exists bistable phenomenon and the tumour cells would be cleared if the effect of chemotherapy on depletion of the tumour cells is strong enough or the side effect of chemotherapy on the hunting predator cells is under a threshold. It is also shown that a branch of stable periodic solutions bifurcates from the coexistence equilibrium when the intrinsic recruitment delay of tumor crosses the threshold which is new mechanism, which can help understand the short-term oscillations in tumour sizes as well as long-term tumour relapse. Numerical simulations are presented to illustrate that larger intrinsic recruitment delay of tumor leads to larger amplitude and longer period of the bifurcated periodic solution, which indicates that there exists longer relapse time and then contributes to the control of tumour growth.

摘要

本文构建了一个包含肿瘤细胞、细胞毒性 T 淋巴细胞、辅助性 T 细胞的三维非线性时滞微分系统,以研究内在招募延迟和化疗的影响。研究发现,化疗和时滞的引入可以在肿瘤免疫系统中产生更丰富的动力学。特别是,存在双稳现象,如果化疗对肿瘤细胞耗竭的作用足够强,或者化疗对狩猎捕食细胞的副作用低于阈值,肿瘤细胞将被清除。研究还表明,当肿瘤的内在招募延迟超过阈值时,从共存平衡点分叉出一条稳定的周期解分支,这是一种新的机制,可以帮助理解肿瘤大小的短期波动以及长期的肿瘤复发。数值模拟表明,较大的肿瘤内在招募延迟会导致分叉周期解的幅度更大、周期更长,这表明复发时间更长,从而有助于控制肿瘤的生长。

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