scholarly journals Potential of Immunotherapies in Treating Hematological Cancer-Infection Comorbidities—A Mathematical Modelling Approach

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3789
Author(s):  
Johnny T. Ottesen ◽  
Morten Andersen
Keyword(s):  
Immune System ◽  
Cancer Progression ◽  
Adaptive Immune System ◽  
Severe Infection ◽  
Hematological Cancer ◽  
Dormant State ◽  
Adaptive Immune ◽  
Cell Immunotherapy ◽  
Car T ◽  
Infection Disease

The immune system protects the human body against threats such as emerging cancers or infections, e.g., COVID-19. Mutated malignant cells may in many cases be controlled by the immune system to be kept at unnoticed low amount. However, a severe infection may compromise the immune system in controlling such malignant clones leading to escape and fatal cancer progression. A novel mechanism based computational model coupling cancer and infection to the adaptive immune system is presented and analyzed. The model pin-points important physiological mechanisms responsible for cancer progression and explains numerous medical observations. The progression of a cancers and the effects of treatments depend on cancer burden, the level of infection and on the efficiency of the adaptive immune system. The model exhibits bi-stability, i.e., gravitate towards one of two stable steady states: a harmless dormant state or a full-blown cancer-infection disease state. A borderline exists and if infection exceeds this for a sufficiently long period of time the cancer escapes. Early treatment is vital for remission and may control the cancer back into the stable dormant state. CAR T-cell immunotherapy is investigated by help of the model. The therapy significantly improves its efficacy in combination with antibiotics or immunomodulation.

Stochastic cancer-immune coevolution: Implications for cancer incidence and immunotherapeutic efficacy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14023-e14023
Author(s):  
Jason T George ◽  
Herbert Levine ◽  
Jeffrey J. Molldrem ◽  
Haven Garber
Keyword(s):  
Immune System ◽  
T Cell ◽  
Cancer Incidence ◽  
Adaptive Immune System ◽  
Turnover Rates ◽  
Cell Repertoire ◽  
Adaptive Immune ◽  
Cell Immunotherapy ◽  
Cell Diversity ◽  
T Cell Immunotherapy

e14023 Background: Despite recent progress, robust treatment strategies that lead to durable remission are still lacking for many cancer types. This disease is difficult to treat owing in part to the complexity introduced by a heterogeneous population of cancer cells capable of evolving mechanisms of resistance to traditional therapy. Nonetheless, the discovery and continued optimization of T-cell immunotherapy has revolutionized the treatment of many cancers. This treatment strategy stands out from other approaches in its unique ability to co-evolve alongside an evading tumor. While promising, such therapies are also complex. For example, allogeneic stem cell transplantation leverages a donor-derived T-cell repertoire to treat patients with refractory hematologic malignancies and relies upon a delicate balance between desirable anti-tumor effects and potentially life-threatening graft-versus-host-disease. Currently, the decision to utilize this therapy and others like it is largely influenced by prior empirical evidence. Thus, there is great need for quantitative models of the cancer-immune interaction to generate testable predictions of treatment outcome, which could then be validated prior to T-cell immunotherapy administration. Methods: We develop a foundational mathematical model to investigate the properties of stochastic tumor-immune co-evolution using applied stochastic process theory and probabilistic analysis. We use this model to predict the effects of reduced immunity, T-cell diversity, and thymic turnover rates on cancer incidence, and compare model simulations to cancer evolutionary data. Results: We predict that changes in T-cell diversity, and to a lesser degree thymic turnover, increase the chance of tumor progression. When applied to experimental data, we demonstrate that the observations are consistent with co-evolution between an indolent cancer population and the adaptive immune system prior to clinical disease. Conclusions: Our results provide a fundamental framework for analyzing the interaction dynamics of an evolving threat like cancer and the adaptive immune system in order to better understand and predict immunotherapeutic efficacy.

The Use of Immune System Cells for The Treatment of Metastatic Cancer: A Personalised Medicine Concept

2021 ◽  
Author(s):  
Olorunfemi Ayeotan
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Metastatic Cancer ◽  
Personalised Medicine ◽  
Adaptive Immune System ◽  
Innate And Adaptive Immunity ◽  
Adaptive Immune ◽  
Immune Attack

Cancer is initiated by an alteration or mutation of genes which may occur naturally i.e., inherited or acquired over the years as a result of environmental factors or by exposure to certain chemicals (carcinogens), exposure to various forms of radiations and lifestyle habit such as smoking, alcohol, poor diet and obesity. During cancer progression, various components of the innate and adaptive immunity are activated in effort to reduce or remove the cancer mediated inflammation but tumour cells avoid the immune attack posed by these cells. Various cancer cells have unique mechanisms through which they escape from the immune response making them resistance to destruction by the immune system. In effort to treat various forms of cancers, scientists have been able to device means by which the immune system can be modified in other to fight cancer cells, this form of treatment that focuses on the modification of the innate and adaptive immune system in treatment of cancer is termed immunotherapy.

Evolution and age characteristics of the innate and adaptive immune system

2016 ◽  
Vol 75 (3) ◽  
pp. 74-84 ◽  
Author(s):  
A.E. Abaturov ◽  
◽  
E.A. Agafonova ◽  
N.I. Abaturova ◽  
V.L. Babich ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Adaptive Immune

scholarly journals Unfolded Protein Corona Surrounding Nanotubes Influence the Innate and Adaptive Immune System

2021 ◽  
Vol 8 (8) ◽  
pp. 2004979
Author(s):  
Jun‐Young Park ◽  
Sung Jean Park ◽  
Jun Young Park ◽  
Sang‐Hyun Kim ◽  
Song Kwon ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Protein Corona ◽  
Unfolded Protein ◽  
Adaptive Immune

scholarly journals T Cells Limit Accumulation of Aggregate Pathology Following Intrastriatal Injection of α-Synuclein Fibrils

2021 ◽  
pp. 1-19
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Substantia Nigra ◽  
Adaptive Immune System ◽  
Proteinase K ◽  
T And B Cells ◽  
Adaptive Immune ◽  
Immunocompromised Mice ◽  
The Impact

Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α- synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.

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