Mathematical Modelling of the Inhibitory Role of Regulatory T Cells in Tumor Immune Response

The immune system against tumors acts through a complex dynamical process showing a dual role. On the one hand, the immune system can activate some immune cells to kill tumor cells (TCs), such as cytotoxic T lymphocytes (CTLs) and natural killer cells (NKs), but on the other hand, more evidence show...

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Main Authors: Zhongtao Yang, Cuihong Yang, Yueping Dong, Yasuhiro Takeuchi
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Complexity
Online Access:http://dx.doi.org/10.1155/2020/4834165
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author Zhongtao Yang
Cuihong Yang
Yueping Dong
Yasuhiro Takeuchi
author_facet Zhongtao Yang
Cuihong Yang
Yueping Dong
Yasuhiro Takeuchi
author_sort Zhongtao Yang
collection DOAJ
description The immune system against tumors acts through a complex dynamical process showing a dual role. On the one hand, the immune system can activate some immune cells to kill tumor cells (TCs), such as cytotoxic T lymphocytes (CTLs) and natural killer cells (NKs), but on the other hand, more evidence shows that some immune cells can help tumor escape, such as regulatory T cells (Tregs). In this paper, we propose a tumor immune interaction model based on Tregs-mediated tumor immune escape mechanism. When helper T cells’ (HTCs) stimulation rate by the presence of identified tumor antigens is below critical value, the coexistence (tumor and immune) equilibrium is always stable in its existence region. When HTCs stimulation rate is higher than the critical value, the inhibition rate of effector cells (ECs) by Tregs can destabilize the coexistence equilibrium and cause Hopf bifurcations and produce a limit cycle. This model shows that Tregs might play a crucial role in triggering the tumor immune escape. Furthermore, we introduce the adoptive cellular immunotherapy (ACI) and monoclonal antibody immunotherapy (MAI) as the treatment to boost the immune system to fight against tumors. The numerical results show that ACI can control TCs more, while MAI can delay the inhibitory effect of Tregs on ECs. The result also shows that the combination of both immunotherapies can control TCs and reduce the inhibitory effect of Tregs better than a single immunotherapy can control.
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spelling doaj-art-e825cc043ab74339997eb2adfb09d9ba2025-08-20T03:21:00ZengWileyComplexity1076-27871099-05262020-01-01202010.1155/2020/48341654834165Mathematical Modelling of the Inhibitory Role of Regulatory T Cells in Tumor Immune ResponseZhongtao Yang0Cuihong Yang1Yueping Dong2Yasuhiro Takeuchi3School of Mathematics and Statistics, Central China Normal University, Wuhan 430079, ChinaSchool of Mathematics and Statistics, Central China Normal University, Wuhan 430079, ChinaSchool of Mathematics and Statistics, Central China Normal University, Wuhan 430079, ChinaCollege of Science and Engineering, Aoyama Gakuin University, Sagamihara 252-5258, JapanThe immune system against tumors acts through a complex dynamical process showing a dual role. On the one hand, the immune system can activate some immune cells to kill tumor cells (TCs), such as cytotoxic T lymphocytes (CTLs) and natural killer cells (NKs), but on the other hand, more evidence shows that some immune cells can help tumor escape, such as regulatory T cells (Tregs). In this paper, we propose a tumor immune interaction model based on Tregs-mediated tumor immune escape mechanism. When helper T cells’ (HTCs) stimulation rate by the presence of identified tumor antigens is below critical value, the coexistence (tumor and immune) equilibrium is always stable in its existence region. When HTCs stimulation rate is higher than the critical value, the inhibition rate of effector cells (ECs) by Tregs can destabilize the coexistence equilibrium and cause Hopf bifurcations and produce a limit cycle. This model shows that Tregs might play a crucial role in triggering the tumor immune escape. Furthermore, we introduce the adoptive cellular immunotherapy (ACI) and monoclonal antibody immunotherapy (MAI) as the treatment to boost the immune system to fight against tumors. The numerical results show that ACI can control TCs more, while MAI can delay the inhibitory effect of Tregs on ECs. The result also shows that the combination of both immunotherapies can control TCs and reduce the inhibitory effect of Tregs better than a single immunotherapy can control.http://dx.doi.org/10.1155/2020/4834165
spellingShingle Zhongtao Yang
Cuihong Yang
Yueping Dong
Yasuhiro Takeuchi
Mathematical Modelling of the Inhibitory Role of Regulatory T Cells in Tumor Immune Response
Complexity
title Mathematical Modelling of the Inhibitory Role of Regulatory T Cells in Tumor Immune Response
title_full Mathematical Modelling of the Inhibitory Role of Regulatory T Cells in Tumor Immune Response
title_fullStr Mathematical Modelling of the Inhibitory Role of Regulatory T Cells in Tumor Immune Response
title_full_unstemmed Mathematical Modelling of the Inhibitory Role of Regulatory T Cells in Tumor Immune Response
title_short Mathematical Modelling of the Inhibitory Role of Regulatory T Cells in Tumor Immune Response
title_sort mathematical modelling of the inhibitory role of regulatory t cells in tumor immune response
url http://dx.doi.org/10.1155/2020/4834165
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