scholarly journals Periodically Pulsed Immunotherapy in a Mathematical Model of Tumor, CD4+ T Cells, and Antitumor Cytokine Interactions

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Hsiu-Chuan Wei ◽  
Jui-Ling Yu ◽  
Chia-Yu Hsu
Keyword(s):  
Mathematical Model ◽  
T Cells ◽  
Immune System ◽  
Interindividual Variability ◽  
Malignant Tumors ◽  
Early Stage ◽  
Bifurcation Diagrams ◽  
Mathematical Analyses ◽  
Cytokine Interactions ◽  
Parameter Bifurcation

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.

scholarly journals Mathematical model of a personalized neoantigen cancer vaccine and the human immune system

2021 ◽  
Vol 17 (9) ◽  
pp. e1009318
Author(s):  
Marisabel Rodriguez Messan ◽  
Osman N. Yogurtcu ◽  
Joseph R. McGill ◽  
Ujwani Nukala ◽  
Zuben E. Sauna ◽  
...  
Keyword(s):  
Mathematical Model ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Cancer Vaccine ◽  
Tumor Size ◽  
Cancer Vaccines ◽  
Patient Specific ◽  
Human Immune System ◽  
Human Immune

Cancer vaccines are an important component of the cancer immunotherapy toolkit enhancing immune response to malignant cells by activating CD4+ and CD8+ T cells. Multiple successful clinical applications of cancer vaccines have shown good safety and efficacy. Despite the notable progress, significant challenges remain in obtaining consistent immune responses across heterogeneous patient populations, as well as various cancers. We present a mechanistic mathematical model describing key interactions of a personalized neoantigen cancer vaccine with an individual patient’s immune system. Specifically, the model considers the vaccine concentration of tumor-specific antigen peptides and adjuvant, the patient’s major histocompatibility complexes I and II copy numbers, tumor size, T cells, and antigen presenting cells. We parametrized the model using patient-specific data from a clinical study in which individualized cancer vaccines were used to treat six melanoma patients. Model simulations predicted both immune responses, represented by T cell counts, to the vaccine as well as clinical outcome (determined as change of tumor size). This model, although complex, can be used to describe, simulate, and predict the behavior of the human immune system to a personalized cancer vaccine.

scholarly journals Non-linear tumor-immune interactions arising from spatial metabolic heterogeneity

2016 ◽  
Author(s):  
Mark Robertson-Tessi ◽  
Robert J. Gillies ◽  
Robert A. Gatenby ◽  
Alexander R. A. Anderson
Keyword(s):  
Mathematical Model ◽  
T Cells ◽  
Immune System ◽  
Tumor Growth ◽  
Cytotoxic T Cells ◽  
Non Linear ◽  
Metabolic Heterogeneity ◽  
Multiscale Mathematical Model ◽  
Tumor Phenotypes

AbstractA hybrid multiscale mathematical model of tumor growth is used to investigate how tumoral and microenvironmental heterogeneity affect the response of the immune system. The model includes vascular dynamics and evolution of metabolic tumor phenotypes. Cytotoxic T cells are simulated, and their effect on tumor growth is shown to be dependent on the structure of the microenvironment and the distribution of tumor phenotypes. Importantly, no single immune strategy is best at all stages of tumor growth.

scholarly journals Data-Driven Mathematical Model of Osteosarcoma

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2367
Author(s):  
Trang Le ◽  
Sumeyye Su ◽  
Arkadz Kirshtein ◽  
Leili Shahriyari
Keyword(s):  
Mathematical Model ◽  
T Cells ◽  
Immune System ◽  
Regulatory T Cells ◽  
Tumor Progression ◽  
Immune Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Decay Rates ◽  
Data Driven

As the immune system has a significant role in tumor progression, in this paper, we develop a data-driven mathematical model to study the interactions between immune cells and the osteosarcoma microenvironment. Osteosarcoma tumors are divided into three clusters based on their relative abundance of immune cells as estimated from their gene expression profiles. We then analyze the tumor progression and effects of the immune system on cancer growth in each cluster. Cluster 3, which had approximately the same number of naive and M2 macrophages, had the slowest tumor growth, and cluster 2, with the highest population of naive macrophages, had the highest cancer population at the steady states. We also found that the fastest growth of cancer occurred when the anti-tumor immune cells and cytokines, including dendritic cells, helper T cells, cytotoxic cells, and IFN-γ, switched from increasing to decreasing, while the dynamics of regulatory T cells switched from decreasing to increasing. Importantly, the most impactful immune parameters on the number of cancer and total cells were the activation and decay rates of the macrophages and regulatory T cells for all clusters. This work presents the first osteosarcoma progression model, which can be later extended to investigate the effectiveness of various osteosarcoma treatments.

scholarly journals Elevated levels and Clinical Association of Serum Cytokines in Untreated HIV-1 Infection

2021 ◽  
Author(s):  
Na Zhang ◽  
Chang-Xin Yan ◽  
Shuang-Mei Yu ◽  
Xiao-Xiong Wang ◽  
Lei Teng ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Hiv Infection ◽  
Early Stage ◽  
Serum Levels ◽  
Underlying Mechanism ◽  
Cell Counts ◽  
Aids Progression ◽  
Hiv 1

Abstract Background Human immunodeficiency virus type 1 (HIV-1) infection disturbs the balance of CD4+ T cells and monocytes in the immune system. In the early stage of infection, the virus stimulates the activation and proliferation of immune cells, induces the release of cytokines, destroys CD4+ T cells, and accelerates HIV-1 replication and AIDS progression. It is essential to explore cytokine changes after HIV-1 infection and further understand the underlying mechanism of HIV infection. Methods In this study, we enrolled 38 HIV-infected subjects and 30 healthy subjects. We measured and compared CD4+ T cell counts and the serum cytokine levels in different groups. Results Our results showed significantly higher serum levels of IL-1β, IL-2, IL-4, IL-7, IL-10, IL-17, IFN-γ, and TNF-α in HIV-infected patients. Higher levels of IL-6 and IL-17 were observed in the < 200/mL CD4+ T cell count group, and higher levels of IL-2 were observed in the CCR5-tropic HIV strain group. Conclusion In conclusion, we found that HIV infection-induced activation of the immune system and cytokines could predict the severity of HIV disease and regulate HIV infection and replication differently depending on the type of virus strain.

scholarly journals Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease

2021 ◽  
Vol 8 (5) ◽  
pp. e1036
Author(s):  
Zhaoqi Yan ◽  
Wei Yang ◽  
Hairong Wei ◽  
Marissa N. Dean ◽  
David G. Standaert ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Parkinson Disease ◽  
Peripheral Blood ◽  
Cytokine Production ◽  
Early Stage ◽  
Adaptive Immune System ◽  
Th2 Cells ◽  
Adaptive Immune

ObjectiveTo determine the activation status and cytokine profiles of CD4+ T cells, CD8+ T cells, and CD19+ B cells from patients with early-stage Parkinson disease (PD) compared with healthy controls (HCs).MethodsPeripheral blood samples from 41 patients with early-stage PD and 40 HCs were evaluated. Peripheral blood mononuclear cells were analyzed by flow cytometry for surface markers and intracellular cytokine production. Correlations of immunologic changes and clinical parameters were analyzed.ResultsAdaptive immunity plays a role in the pathogenesis of PD, yet the contribution of T cells and B cells, especially cytokine production by these cells, is poorly understood. We demonstrate that naive CD4+ and naive CD8+ T cells are significantly decreased in patients with PD, whereas central memory CD4+ T cells are significantly increased in patients with PD. Furthermore, IL-17–producing CD4+ Th17 cells, IL-4–producing CD4+ Th2 cells, and IFN-γ–producing CD8+ T cells are significantly increased in patients with PD. Regarding B cells, we observed a decrease in naive B cells and an increase in nonswitched memory and double-negative B cells. As well, TNF-α–producing CD19+ B cells were significantly increased in patients with PD. Notably, some of the changes observed in CD4+ T cells and B cells were associated with clinical motor disease severity.ConclusionsThese findings suggest that alterations in the adaptive immune system may promote clinical disease in PD by skewing to a more proinflammatory state in the early-stage PD patient cohort. Our study may shed light on potential immunotherapies targeting dysregulated CD4+ T cells, CD8+ T cells, and CD19+ B cells in patients with PD.

scholarly journals Stability Analysis of Mathematical Model including Pathogen-Specific Immune System Response with Fractional-Order Differential Equations

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bahatdin Daşbaşı
Keyword(s):  
Mathematical Model ◽  
T Cells ◽  
Immune System ◽  
Qualitative Analysis ◽  
Fractional Order ◽  
Memory T Cells ◽  
Equilibrium Points ◽  
System Response ◽  
Proposed Model ◽  
The Mathematical Model

In this study, the mathematical model examined the dynamics between pathogen and specific immune system cells (memory T cells) for diseases such as chronic infection and cancer in which nonspecific immune system cells are inadequate to destroy the pathogen and has been suggested by using a system of the fractional-order differential equation with multi-orders. Qualitative analysis of the proposed model reveals the equilibrium points giving important ideas about the proliferation of the pathogen and memory T cells. According to the results of this analysis, the possible scenarios are as follows: the absence of both pathogen and memory T cells, only the existence of pathogen, and the existence of both pathogen and memory T cells. The qualitative analysis of the proposed model has expressed the persistent situations of the disease where the memory T cells either do not be able to respond to the pathogen or continue to exist with the disease-causing pathogen in the host. Results of this analysis are supported by numerical simulations. In the simulations, the time-dependent size of the tumor population under the pressure of the memory T cells was tried to be estimated.

scholarly journals Achievements and prospects of cellular technologies based on the activated lymphocytes in the treatment of malignant tumors

2018 ◽  
Vol 99 (5) ◽  
pp. 792-801 ◽  
Author(s):  
E Yu Zlatnik ◽  
A O Sitkovskaya ◽  
E M Nepomnyashchaya ◽  
Ph R Dzhandigova ◽  
L N Vashchenko
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
T Lymphocytes ◽  
Adoptive Immunotherapy ◽  
Malignant Tumors ◽  
The Body ◽  
Cellular Immunotherapy ◽  
Cytotoxic Lymphocytes ◽  
Activated Lymphocytes

This article reviews the immune system and its role in the relationship between the tumor and the body of a patient with tumor diseases. It is about controlling homeostasis by recognizing and eliminating genetically alien substances (antigens). Antitumor treatment is now not only considered as an “instrument” for eliminating and destroying tumor cells, but also its ability to change/restore impaired functions of the immune system attracts attention. The used antitumor treatment is widely known to be immunosuppressive, stress and radiation effects also cause and/or enhance immunosuppression. In this work, the authors provide literature data demonstrating current status and problems of cellular immunotherapy of malignant tumors with the use of activated lymphocytes, and the role of antigen-specific T-lymphocytes as one of its most important agents is reviewed. Currently, among the immunotherapeutic methods, a special place is occupied by approaches involving the use of autologous or allogenic ex vivo stimulated immunocompetent cells (adoptive immunotherapy). The importance of complex influence on various links (T-, B-, NK-cell) and stages (presentation, recognition, proliferation, differentiation, migration, activation, effector functions) of the immune response is considered. The emergence of targeted drugs based on antibodies, as well as vaccines, especially dendritic cells, has provoked the emergence of a new wave of interest in the formation of specific antitumoral immune response mediated by T lymphocytes, so the introduction of the latter can be classified as a kind of targeted therapy. The value of antigen-specific T-lymphocytes in the formation of antitumor immunity is shown, which emphasizes the importance not only of CD8+, but also of CD4+ T-lymphocytes. In addition, there are suggestions of the possible significance of both T- and B-cells for developing a strategy of cellular immunotherapy. The literature data suggest that not only cytotoxic lymphocytes, but also T-helpers and even B-lymphocytes can be effective as antigen-specific lymphocytes as a component of antitumor treatment. The authors consider the possibility of obtaining antigen-specific T cells, as well as their further storage. The possibility of elimination or selective inhibition of regulatory T-cells during adoptive immunotherapy aimed at removing the suppressor effect on cytotoxic lymphocytes is studied. Various strategies for the use of cell therapy are also discussed.

Novel Coronavirus SARS-CoV-2 (COVID-19) and Pregnancy: A hypothetical view

2020 ◽  
Vol 20 ◽  
Author(s):  
Ahmed RG
Keyword(s):  
Immune System ◽  
Cellular Therapy ◽  
Early Stage ◽  
Control Strategies ◽  
Vital Role ◽  
Healthy Life ◽  
Global Pandemic ◽  
Maternal Immune System ◽  
Perinatal Management ◽  
Novel Coronavirus

Background: The complications of the SARS-CoV-2 infection and its COVID-19 disease on mothers and their offspring are less known. Objective: The aim of this review was to determine the transmission, severity, complications of SARS-CoV-2 infection during the pregnancy. This review showed the influence of COVID-19 disease on the neonatal neurogenesis. Owing to no specific vaccines or medicines that were reported for the treatment of COVID-19 disease, this review suggested some control strategies like treatments (medicinal plants, antiviral therapy, cellular therapy, and immunotherapy), nutrition uptake, prevention, and recommendations. Discussion: This overview showed in severely states that SARS-CoV-2 infection during the early stage of pregnancy might increase the risk of stress, panic, and anxiety. This disorder can disturb the maternal immune system, and thus causing a neurodevelopmental disturbance. This hypothesis may be depending on the severity and intensity of the SARS-CoV-2 infection during pregnancy. However, vertical transmission of SARS-CoV-2 from dams to their fetuses is absent until now. Conclusion: During this global pandemic disease, maintaining safety during pregnancy, vaginal delivery, and breastfeeding may play a vital role in a healthy life for the offspring. Thus, international and national corporations should be continuing for perinatal management, particularly during the next pandemic or disaster time.

scholarly journals Chronic low-level cadmium exposure in rats affects cytokine production by activated T cells

2019 ◽  
Vol 8 (2) ◽  
pp. 227-237 ◽  
Author(s):  
Alexandra E. Turley ◽  
Joseph W. Zagorski ◽  
Rebekah C. Kennedy ◽  
Robert A. Freeborn ◽  
Jenna K. Bursley ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Low Dose ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Cadmium Exposure ◽  
Activated T Cells ◽  
Low Level

The purpose of this study was to determine the effect of subchronic, oral, low-dose cadmium exposure (32 ppm over 10 weeks) on the rat immune system. We found that cadmium exposure increased the induction of IFNγ and IL-10 in T cells activated ex vivo after cadmium exposure.

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