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The role of CD4⁺ T cells in tumor and chronic viral immune responses.

ABSTRACT: Immunotherapies are mainly aimed to promote a CD8⁺ T cell response rather than a CD4⁺ T cell response as cytotoxic T lymphocytes (CTLs) can directly kill target cells. Recently, CD4⁺ T cells have received more attention due to their diverse roles in tumors and chronic viral infections. In antitumor and antichronic viral responses, CD4⁺ T cells relay help signals through dendritic cells to indirectly regulate CD8⁺ T cell response, interact with B cells or macrophages to indirectly modulate humoral immunity or macrophage polarization, and inhibit tumor blood vessel formation. Additionally, CD4⁺ T cells can also exhibit direct cytotoxicity toward target cells. However, regulatory T cells exhibit immunosuppression and CD4⁺ T cells become exhausted, which promote tumor progression and chronic viral persistence. Finally, we also outline immunotherapies based on CD4⁺ T cells, including adoptive cell transfer, vaccines, and immune checkpoint blockade. Overall, this review summarizes diverse roles of CD4⁺ T cells in the antitumor or protumor and chronic viral responses, and also highlights the immunotherapies based on CD4⁺ T cells, giving a better understanding of their roles in tumors and chronic viral infections.

SUBMITTER: Xie L

PROVIDER: S-EPMC10565399 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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The role of CD4+ T cells in tumor and chronic viral immune responses.

Xie Luoyingzi L Fang Jingyi J Yu Juncheng J Zhang Weinan W He Zhiqiang Z Ye Lilin L Wang Huaizhi H

MedComm 20231010 5

Immunotherapies are mainly aimed to promote a CD8+ T cell response rather than a CD4+ T cell response as cytotoxic T lymphocytes (CTLs) can directly kill target cells. Recently, CD4+ T cells have received more attention due to their diverse roles in tumors and chronic viral infections. In antitumor and antichronic viral responses, CD4+ T cells relay help signals through dendritic cells to indirectly regulate CD8+ T cell response, interact wi ...[more]

PMID: 37829505

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Project description:Mathematical modelling has been used to study tumor-immune cell interaction. Some models were proposed to examine the effect of circulating lymphocytes, natural killer cells, and CD8+T cells, but they neglected the role of CD4+T cells. Other models were constructed to study the role of CD4+T cells but did not consider the role of other immune cells. In this study, we propose a mathematical model, in the form of a system of nonlinear ordinary differential equations, that predicts the interaction between tumor cells and natural killer cells, CD4+T cells, CD8+T cells, and circulating lymphocytes with or without immunotherapy and/or chemotherapy. This system is stiff, and the Runge-Kutta method failed to solve it. Consequently, the "Adams predictor-corrector" method is used. The results reveal that the patient's immune system can overcome small tumors; however, if the tumor is large, adoptive therapy with CD4+T cells can be an alternative to both CD8+T cell therapy and cytokines in some cases. Moreover, CD4+T cell therapy could replace chemotherapy depending upon tumor size. Even if a combination of chemotherapy and immunotherapy is necessary, using CD4+T cell therapy can better reduce the dose of the associated chemotherapy compared to using combined CD8+T cells and cytokine therapy. Stability analysis is performed for the studied patients. It has been found that all equilibrium points are unstable, and a condition for preventing tumor recurrence after treatment has been deduced. Finally, a bifurcation analysis is performed to study the effect of varying system parameters on the stability, and bifurcation points are specified. New equilibrium points are created or demolished at some bifurcation points, and stability is changed at some others. Hence, for systems turning to be stable, tumors can be eradicated without the possibility of recurrence. The proposed mathematical model provides a valuable tool for designing patients' treatment intervention strategies.

Dataset Information

The role of CD4⁺ T cells in tumor and chronic viral immune responses.

Publications

The role of CD4<sup>+</sup> T cells in tumor and chronic viral immune responses.

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