Anderson2015 - Qualitative behavior of systems of tumor-CD4+-cytokine interactions with treatments
Ontology highlight
ABSTRACT:
SUBMITTER: 
Johannes Meyer
PROVIDER: BIOMD0000000813 | BioModels | 2019-09-17
REPOSITORIES: BioModels
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Project description:This is a proposed mathematical model describing interactions between tumor cells, CD4+ T cells, cytokines, and host cells within the context of CD4+ T cells inducing tumor regression. A platform is provided to assess the effectiveness of single or combination therapy with CD4+ T cells and/or cytokines.
2021-10-05 | BIOMD0000000797 | BioModels
Project description:This ordinary differential equation model simulating the interactions between tumor and immune cells is detailed in the publication:
Ahmed M. Makhlouf, Lamiaa El-Shennawy, Hesham A. Elkaranshawy, "Mathematical Modelling for the Role of CD4+T Cells in Tumor-Immune Interactions", Comput Math Methods Med. 2020 Feb 19;2020:7187602.
doi: 10.1155/2020/7187602
Comment:
This no treatment model is described by equations 1-7 of the publication manuscript.
Abstract:
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.
2021-09-06 | BIOMD0000001042 | BioModels
Project description:Human Colonic CD4 T cells consist of several subsets differing in their expression of CD161. We exposed these cells to either cytokine, TCR or combined stimulation and assessed the subsequent changes in gene and protein expression with an emphasis on cytokine receptors and gene associated with tissue repair.
2022-07-02 | GSE207159 | GEO
Project description:This experiment was designed to study the cytokine gene expression profile of macrophage under 50uM DU exposure. the experiment was repeated three time, with duplicate spots for each gene on the array. Conclusion: DU exposure induces the expressions of IL-10, NF-kBP65, and Midkine and other cytokine genes, indicating the immunomodulation abilities of DU. (GSM43230-GSM43241) This experiment was designed to study the cytokine gene expression of splenic CD4+ T-cells under 100uM DU exposure in 24 hours. Conclusion: DU induces Th2 cytokine gene expression (eg. IL-5), and midkine, as well as other cytokine genes, indicating the abilities of DU in promoting Th2 shifting during differtiation. (GSM43242 to GSM43253)
2010-06-10 | E-GEOD-2333 | biostudies-arrayexpress
Project description:Adoptive transfer of CD4+ T cells (TRP-1 CD4+ T cells) specific for tyrp-1 (tyrosinase-related protein 1) eradicate established tumors (melanoma) in lymphopenic RAG-/- hosts. In vitro differentiated CD8+ T cells have been the primary focus of immunotherapy of cancer with little focus on CD4+ T cells. Immunotherapy involving in vitro differentiated T cells given after lymphodepleting regimens significantly augments antitumor immunity in animals and human patients with cancer. However, the mechanisms by which lymphopenia augments adoptive cell therapy and the means of properly differentiating T cells in vitro are still emerging. We demonstrate that naïve tumor/self-specific CD4+ T cells naturally differentiated into T helper type 1 (Th1) cytotoxic T cells in vivo and caused the regression of established tumors and depigmentation in lymphopenic hosts. Therapy was independent of vaccination, exogenous cytokine support, CD8+-, B-, NK and NK-T cells. Proper activation of CD4+ T cells in vivo was important for tumor clearance as naïve tumor-specific CD4+ T cells could not completely treat tumor in lymphopenic common gamma chain-deficient (gc-/-) hosts. gc signaling in the tumor-bearing host was important for survival and proper differentiation of adoptively transferred tumor-specific CD4+ T cells. Thus, these data provide a platform for designing immunotherapies that incorporate tumor/self-reactive CD4+ T cells. 2 x 10^5 sorted TRP-1 CD4+ T cells were transferred i.v. into tumor-bearing RAG-/- hosts on day 7-10 after tumor challenge, and ~1 x 10^6 CD4+ T cells were isolated 1 week later by flow sorting from pooled lymph nodes (LN) or spleens. Dye-swaps were performed.
2010-01-14 | E-GEOD-19904 | biostudies-arrayexpress
Project description:Expression data from cytokine producing human CD4+ T cells
| PRJNA489203 | ENA
Project description:Although CD4 T cell senescence plays an important role in immunosenescence, the mechanism behind this process remains unclear. Here we show that T cell-specific Menin deficiency results in the premature senescence of CD4 T cells, which is accompanied by the senescence-associated secretory phenotype after antigenic stimulation and dysregulated cytokine production. Menin is required for the expansion and survival of antigen-stimulated CD4 T cells in vivo and acts by targeting Bach2, which is known to regulate immune homeostasis and cytokine production. Menin binds to the Bach2 locus, and controls its expression through maintenance of histone acetylation. Menin binding at the Bach2 locus and the Bach2 expression are decreased in the senescent CD4 T cells. These findings reveal a critical role of the Menin-Bach2 pathway in regulating CD4 T cell senescence and cytokine homeostasis, thus indicating the involvement of this pathway in the inhibition of immunosenescence. Gene expression in Menin WT-TH and Menin KO-TH
2014-03-27 | E-GEOD-49968 | biostudies-arrayexpress
Project description:Efficacy of immune checkpoint inhibitors in cancer can be limited by dysfunction of CD8 T cells or down-regulation of HLA class I. Tumor control mechanisms independent of the CD8/HLA-I axis would bypass these limitations. CD4 cytotoxic T lymphocytes (CTLs) have been detected in diverse human cancers. However, their independent roles in tumor immunity are underexplored. Here, we report CD4 T cell-dependent spontaneous tumor regression and subsequent memory responses in a humanized immune system (HIS) mouse model. HT-29 tumors, which upregulate HLA class II expression in response to IFN-γ, regressed or were eliminated in a subset of tumor implanted HIS mice. Mice with regressing tumors showed increased cytotoxic CD4 T cells in blood and tumors and enhanced HLA-II expression on tumor cells compared to mice with progressing tumors. The intratumoral CD4 T cell subset associated with tumor regression expressed multiple cytotoxic markers and exhibited clonal expansion. Notably, tumor control was abrogated by depletion of CD4 but not CD8 T cells. CD4 T cells derived from tumor-regressing mice exhibited HLA-II-dependent and tumor cell-specific killing ex vivo. Taken together, our study demonstrates a critical role of human CD4 CTLs in mediating potent tumor control independent of CD8 T cells and provides a novel platform to study human CD4 CTL-mediated anti-tumor immunity.
2023-01-22 | GSE223026 | GEO
Project description:This experiment was designed to study the cytokine gene expression profile of macrophage under 50uM DU exposure. the experiment was repeated three time, with duplicate spots for each gene on the array. Conclusion: DU exposure induces the expressions of IL-10, NF-kBP65, and Midkine and other cytokine genes, indicating the immunomodulation abilities of DU. (GSM43230-GSM43241) This experiment was designed to study the cytokine gene expression of splenic CD4+ T-cells under 100uM DU exposure in 24 hours. Conclusion: DU induces Th2 cytokine gene expression (eg. IL-5), and midkine, as well as other cytokine genes, indicating the abilities of DU in promoting Th2 shifting during differtiation. (GSM43242 to GSM43253)
2005-02-25 | GSE2333 | GEO
Project description:The paper describes a model of tumor-immune interaction.
Created by COPASI 4.25 (Build 207)
This model is described in the article:
Periodically Pulsed Immunotherapy in a Mathematical Model of Tumor, CD4+ T Cells, and Antitumor Cytokine Interactions
Hsiu-Chuan Wei, Jui-Ling Yu, Chia-Yu Hsu
Computational and Mathematical Methods in Medicine Volume 2017, Article ID 2906282, 12 pages
Abstract:
Immunotherapy is one of the most recent approaches for controlling and curing malignant tumors. In this paper, we consider a mathematical model of periodically pulsed immunotherapy using CD4+ T cells and an antitumor cytokine. Mathematical analyses are performed to determine the threshold of a successful treatment. The interindividual variability is explored by one-, two-, and three-parameter bifurcation diagrams for a nontreatment case. Numerical simulation conducted in this paper shows that (i) the tumor can be regulated by administering CD4+ T cells alone in a patient with a strong immune system or who has been diagnosed at an early stage, (ii) immunotherapy with a large amount of an antitumor cytokine can boost the immune system to remit or even to suppress tumor cells completely, and (iii) through polytherapy the tumor can be kept at a smaller size with reduced dosages.
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2019-08-05 | BIOMD0000000778 | BioModels