scholarly journals Molecular Pathogenesis of Hodgkin Lymphoma: Past, Present, Future

2020 ◽  
Vol 21 (18) ◽  
pp. 6623 ◽  
Author(s):  
Marc Bienz ◽  
Salima Ramdani ◽  
Hans Knecht
Keyword(s):  
Immune System ◽  
Targeted Therapy ◽  
Signaling Pathways ◽  
Hodgkin Lymphoma ◽  
Genetic Instability ◽  
Host Immune System ◽  
Cellular Interactions ◽  
Classical Hodgkin Lymphoma ◽  
The Past

Our understanding of the tumorigenesis of classical Hodgkin lymphoma (cHL) and the formation of Reed–Sternberg cells (RS-cells) has evolved drastically in the last decades. More recently, a better characterization of the signaling pathways and the cellular interactions at play have paved the way for new targeted therapy in the hopes of improving outcomes. However, important gaps in knowledge remain that may hold the key for significant changes of paradigm in this lymphoma. Here, we discuss the past, present, and future of cHL, and review in detail the more recent discoveries pertaining to genetic instability, anti-apoptotic signaling pathways, the tumoral microenvironment, and host-immune system evasion in cHL.

scholarly journals Molecular biology of Hodgkin lymphoma

Leukemia ◽  
2021 ◽  
Vol 35 (4) ◽  
pp. 968-981
Author(s):  
Marc A. Weniger ◽  
Ralf Küppers
Keyword(s):  
B Cells ◽  
B Cell ◽  
Signaling Pathways ◽  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Bacterial Antigen ◽  
Cellular Interactions ◽  
Constitutive Activation ◽  
Expression Program ◽  
Hodgkin Cells

AbstractClassical Hodgkin lymphoma (cHL) is unique among lymphoid malignancies in several key biological features. (i) The Hodgkin and Reed-Sternberg (HRS) tumor cells are rare among an extensive and complex microenvironment. (ii) They derive from B cells, but have largely lost the B-cell typical gene expression program. (iii) Their specific origin appears to be pre-apoptotic germinal center (GC) B cells. (iv) They consistently develop bi- or multinucleated Reed-Sternberg cells from mononuclear Hodgkin cells. (v) They show constitutive activation of numerous signaling pathways. Recent studies have begun to uncover the basis of these specific features of cHL: HRS cells actively orchestrate their complex microenvironment and attract many distinct subsets of immune cells into the affected tissues, to support their survival and proliferation, and to create an immunosuppressive environment. Reed-Sternberg cells are generated by incomplete cytokinesis and refusion of Hodgkin cells. Epstein-Barr virus (EBV) plays a major role in the rescue of crippled GC B cells from apoptosis and hence is a main player in early steps of lymphomagenesis of EBV+ cHL cases. The analysis of the landscape of genetic lesions in HRS cells so far did not reveal any highly recurrent HRS cell-specific lesions, but major roles of genetic lesions in members of the NF-κB and JAK/STAT pathways and of factors of immune evasion. It is perhaps the combination of the genetic lesions and the peculiar cellular origin of HRS cells that are disease defining. A combination of such genetic lesions and multiple cellular interactions with cells in the microenvironment causes the constitutive activation of many signaling pathways, often interacting in complex fashions. In nodular lymphocyte predominant Hodgkin lymphoma, the GC B cell-derived tumor cells have largely retained their typical GC B-cell expression program and follicular microenvironment. For IgD-positive cases, bacterial antigen triggering has recently been implicated in early stages of its pathogenesis.

scholarly journals Potential Roles of Fungal Extracellular Vesicles during Infection

mSphere ◽  
2016 ◽  
Vol 1 (4) ◽  
Author(s):  
Luna S. Joffe ◽  
Leonardo Nimrichter ◽  
Marcio L. Rodrigues ◽  
Maurizio Del Poeta
Keyword(s):  
Immune System ◽  
Extracellular Vesicles ◽  
Virulence Factors ◽  
Cell Types ◽  
Fungal Diseases ◽  
Host Immune System ◽  
The Past ◽  
Invasive Fungal Diseases

ABSTRACT Extracellular vesicles (EVs) are produced by virtually all cell types. Within the past few years, work in this field has revealed more information about fungal EVs. Fungal EVs have been shown to carry proteins, lipids, pigments, polysaccharides, and RNA; these components are known virulence factors, a fact which supports the hypothesis that fungal EVs concentrate pathogenic determinants. Extracellular vesicles (EVs) are produced by virtually all cell types. Within the past few years, work in this field has revealed more information about fungal EVs. Fungal EVs have been shown to carry proteins, lipids, pigments, polysaccharides, and RNA; these components are known virulence factors, a fact which supports the hypothesis that fungal EVs concentrate pathogenic determinants. Additionally, recent studies have demonstrated that fungal EVs stimulate the host immune system. In this review, putative roles of fungal EVs are discussed, including their potential as vaccination tools and their possible contribution to pathogenesis in invasive fungal diseases.

scholarly journals Chagas Disease: Still Many Unsolved Issues

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
José M. Álvarez ◽  
Raissa Fonseca ◽  
Henrique Borges da Silva ◽  
Cláudio R. F. Marinho ◽  
Karina R. Bortoluci ◽  
...  
Keyword(s):  
Heart Disease ◽  
Immune System ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Innate Immune System ◽  
Innate Immune ◽  
Host Immune System ◽  
Immune Effector ◽  
The Past ◽  
Chronic Heart Disease

Over the past 20 years, the immune effector mechanisms involved in the control ofTrypanosoma cruzi, as well as the receptors participating in parasite recognition by cells of the innate immune system, have been largely described. However, the main questions on the physiopathology of Chagas disease remain unanswered: “Why does the host immune system fail to provide sterile immunity?” and “Why do only a proportion of infected individuals develop chronic pathology?” In this review, we describe the mechanisms proposed to explain the inability of the immune system to eradicate the parasite and the elements that allow the development of chronic heart disease. Moreover, we discuss the possibility that the inability of infected cardiomyocytes to sense intracellularT. cruzicontributes to parasite persistence in the heart and the development of chronic pathology.

scholarly journals Molecular Analysis of Elements of Melanoma Insensitivity to TCR-Engineered Adoptive Cell Therapy

2021 ◽  
Vol 22 (21) ◽  
pp. 11726
Author(s):  
Ali R. Jazirehi
Keyword(s):  
T Cells ◽  
Immune System ◽  
Targeted Therapy ◽  
T Cell ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Ex Vivo ◽  
Adoptive Cell Therapy ◽  
High Rate ◽  
Host Immune System

Metastatic melanoma accounts for the highest number of skin cancer-related deaths. Traditional treatments are ineffective due to their inability to induce tumor regression at a high rate. Newer treatments such as immune checkpoint inhibitors (ICI), targeted therapy (BRAFi and MEKi), and T cell receptor (TCR)-engineered T cells aim to increase the ability of the host immune system to recognize and eradicate tumors. ICIs inhibit negative regulatory mechanisms and boost the antitumor activity of the host’s immune system, while targeted therapy directed against aberrant signaling molecules (BRAF and MEK) will block the uncontrolled proliferation and expansion of melanomas. The basis of the TCR-engineered T cell strategy is to transduce host T cells with antigen-specific TCRα/β chains to produce high-affinity T cells for tumor-associated antigens. TCR-transgenic T cells are expanded and activated ex vivo and reinfused into patients to increase the targeting of cancer cells. While these treatments have had varyingly favorable results, their efficacy is limited due to inherent or acquired resistance. Various mechanisms explain melanoma immune-resistance, including the loss or downregulation of the MCH/peptide complex, aberrant activity of signaling pathways, and altered dynamics of apoptotic machinery. Collectively, these mechanisms confer melanoma resistance to apoptotic stimuli delivered by T cells despite a fully functional and effective antitumor immune response. Identification of biomarkers, combination treatment, and the use of CAR T cells are among the approaches that can potentially circumvent melanoma’s resistance to immunotherapy.

scholarly journals Mining the Gut Microbiota for Microbial-Based Therapeutic Strategies in Cancer Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Bolei Li ◽  
Tao Gong ◽  
Yu Hao ◽  
Xuedong Zhou ◽  
Lei Cheng
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Cancer Immunotherapy ◽  
Critical Role ◽  
Therapeutic Strategies ◽  
Host Immune System ◽  
The Past ◽  
Promising Strategy

The past two decades witnessed a revolution in our understanding of host–microbiota interactions that led to the concept of the super-organism consisting of a eukaryotic part and a prokaryotic part. Owing to the critical role of gut microbiota in modulating the host immune system, it is not beyond all expectations that more and more evidence indicated that the shift of gut microbiota influenced responses to numerous forms of cancer immunotherapy. Therapy targeting gut microbiota is becoming a promising strategy to improve cancer immunotherapy. In this review, we discuss the role of the gut microbiota in response to cancer immunotherapy, the mechanisms that the gut microbiota influences cancer immunotherapy, and therapeutic strategies targeting gut microbiota to improve cancer immunotherapy.

scholarly journals Immunopathogenesis of severe acute respiratory syndrome coronavirus-2: evolving knowledge and its current statuss

2021 ◽  
Author(s):  
Nitin Saksena ◽  
Srinivasa Reddy Bonam ◽  
Monica Miranda-Saksena
Keyword(s):  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Current Knowledge ◽  
Host Immune System ◽  
The Past ◽  
Short Space ◽  
Shed Light ◽  
Global Research

As the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is a new virus, the current knowledge on the immunopathogenesis of this newly emerged SARS-CoV-2 is beginning to unravel with intensive ongoing global research efforts. Although a plethora of new studies have been published in a short space of time describing how the virus causes disease and incurs insults on the host immune system and the underlying immunopathogenic mechanisms remain to be elucidated. Thus, the discussion in this review is based on the most current knowledge on the immunopathogenesis of SARS-CoV-2 that has emerged in the past 12 months. The main objective is to shed light on the most current concepts in immunopathological aspects of the lung, bloodstream, and brain caused by the SARS-CoV-2, which has led to the current pandemic resulting in > 100 million infections and > 2 million deaths, and ongoing.

ON A KINETIC (CELLULAR) THEORY FOR COMPETITION BETWEEN TUMORS AND THE HOST IMMUNE SYSTEM

1996 ◽  
Vol 04 (04) ◽  
pp. 479-502 ◽  
Author(s):  
N. BELLOMO ◽  
L. PREZIOSI ◽  
G. FORNI
Keyword(s):  
Immune System ◽  
Statistical Mechanics ◽  
Evolution Equations ◽  
Kinetic Modelling ◽  
Host Immune System ◽  
Cellular Interactions ◽  
Immune Defence ◽  
Qualitative Properties ◽  
Defence System ◽  
The One

This paper deals with a kinetic modelling of the cellular dynamics of tumors interacting with an active immune defence system. The analysis starts from a detailed modelling of the cellular interactions and follows with the derivation of evolution equations in a framework similar to the one of nonlinear statistical mechanics. A discussion about the qualitative properties of the model and on the possibility of its application in immunology is proposed in the last part of the paper.

Nivolumab induces impressive responses in relapsed/refractory classic Hodgkin lymphoma: Single institutional experience

2018 ◽  
Vol 25 (7) ◽  
pp. 1586-1589 ◽  
Author(s):  
Reyad Dada ◽  
Yazeed Zabani
Keyword(s):  
Immune System ◽  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Single Agent ◽  
Classical Hodgkin Lymphoma ◽  
Activated T Cells ◽  
Serious Adverse Events ◽  
Large Patient ◽  
Heavily Pretreated ◽  
Pretreated Patients

ObjectivesCancer can escape the immune system through different mechanisms. One such mechanism is the expression of program death ligand-1 which binds to PD-1 receptor on activated T cells, subsequently leading to inhibition of the immune response against cancer cells. Nivolumab is a novel antibody that binds to PD-1 and prevents such immune tolerance. Two recently published controlled clinical trials confirmed the clinical efficacy of single-agent nivolumab in pretreated patients with classical Hodgkin lymphoma.Patients and methodsWe treated 10 heavily pretreated patients with classical Hodgkin lymphoma with the new novel PD-1 inhibitor nivolumab. We report on the outcome and safety of this agent in these patients.ResultsAfter four cycles, the response rate was 80%. Seven of 10 gained complete metabolic remission. No serious adverse events were observed. The available literature is being reviewed.ConclusionsPretreated classical Hodgkin lymphoma is amenable to novel immunotherapy. Nivolumab induces clinically meaningful responses with excellent tolerability. The drug enriches our treatment options by reviving the response of the immune system against cancer. Further controlled studies are needed to determine the effectiveness on a large patient cohort.

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