scholarly journals A bi-directional dialog between vascular cells and monocytes/macrophages regulates tumor progression

2021 ◽  
Author(s):  
Victor Delprat ◽  
Carine Michiels
Keyword(s):  
Tumor Progression ◽  
Cancer Progression ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
The Body ◽  
Vascular Cells ◽  
Tumor Associated Macrophage ◽  
Immune Cell Activation ◽  
The Impact

AbstractCancer progression largely depends on tumor blood vessels as well on immune cell infiltration. In various tumors, vascular cells, namely endothelial cells (ECs) and pericytes, strongly regulate leukocyte infiltration into tumors and immune cell activation, hence the immune response to cancers. Recently, a lot of compelling studies unraveled the molecular mechanisms by which tumor vascular cells regulate monocyte and tumor-associated macrophage (TAM) recruitment and phenotype, and consequently tumor progression. Reciprocally, TAMs and monocytes strongly modulate tumor blood vessel and tumor lymphatic vessel formation by exerting pro-angiogenic and lymphangiogenic effects, respectively. Finally, the interaction between monocytes/TAMs and vascular cells is also impacting several steps of the spread of cancer cells throughout the body, a process called metastasis. In this review, the impact of the bi-directional dialog between blood vascular cells and monocytes/TAMs in the regulation of tumor progression is discussed. All together, these data led to the design of combinations of anti-angiogenic and immunotherapy targeting TAMs/monocyte whose effects are briefly discussed in the last part of this review.

scholarly journals Epithelial–mesenchymal transition: role in cancer progression and the perspectives of antitumor treatment

Acta Naturae ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 4-23
Author(s):  
A. V. Gaponova ◽  
S. Rodin ◽  
A. A. Mazina ◽  
P. V. Volchkov
Keyword(s):  
Epithelial Cells ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
The Body ◽  
Epithelial Tissue ◽  
Mesenchymal Transition ◽  
Tumor Dissemination

About 90% of all malignant tumors are of epithelial nature. The epithelial tissue is characterized by a close interconnection between cells through cellcell interactions, as well as a tight connection with the basement membrane, which is responsible for cell polarity. These interactions strictly determine the location of epithelial cells within the body and are seemingly in conflict with the metastatic potential that many cancers possess (the main criteria for highly malignant tumors). Tumor dissemination into vital organs is one of the primary causes of death in patients with cancer. Tumor dissemination is based on the so-called epithelialmesenchymal transition (EMT), a process when epithelial cells are transformed into mesenchymal cells possessing high mobility and migration potential. More and more studies elucidating the role of the EMT in metastasis and other aspects of tumor progression are published each year, thus forming a promising field of cancer research. In this review, we examine the most recent data on the intracellular and extracellular molecular mechanisms that activate EMT and the role they play in various aspects of tumor progression, such as metastasis, apoptotic resistance, and immune evasion, aspects that have usually been attributed exclusively to cancer stem cells (CSCs). In conclusion, we provide a detailed review of the approved and promising drugs for cancer therapy that target the components of the EMT signaling pathways.

9 METABOLIC UTILIZATION OF PROPANEDIOL BY ADHERENT-INVASIVE E. COLI REGULATES INTESTINAL TISSUE IMMUNITY

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S33-S33
Author(s):  
Monica Viladomiu ◽  
Maeva Metz ◽  
Svetlana Lima ◽  
Chun-Jun Guo ◽  
Kenneth Simpson ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Th17 Cells ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Mononuclear Phagocytes ◽  
Secretion Systems ◽  
E Coli ◽  
Immune Cell Activation

Abstract While the molecular mechanisms by which the microbiome modulates mucosal immunity in Crohn’s disease (CD) are still largely unknown, recent data highlight the involvement of specific diet- and bacterial-derived metabolites in the regulation of intestinal immune cell activation and differentiation. We have recently shown that Adherent-Invasive E.coli (AIEC), which are enriched in CD patients, are sufficient to induce intestinal Th17 cells. Although AIEC lack pathogenic factors including type III secretion systems, many CD-derived isolates express virulence-associated metabolic enzymes including propanediol dehydratase (PduC), which enables AIEC to use fucose-derived propanediol as an alternate carbon source in the gut. We found that pduC is enriched in the microbiome and among E. coli genomes in CD patients compared to healthy controls. With fucosylated oligosaccharides on the surface of intestinal epithelial cells, we hypothesized that this propanediol utilization pathway provides AIEC a competitive advantage for epithelial cell adherence and intestinal immune cell activation. To evaluate the physiologic contribution of pduC to mucosal Th17 induction, we generated a pduC-deficient (ΔpduC) mutant of a CD-derived, AIEC isolate. Deletion of pduC resulted in reduced inflammatory Th17 cells and attenuated weight loss following T cell transfer colitis. Using genetic mouse models, we found that CX3CR1+ mononuclear phagocytes are required for this AIEC-mediated Th17 induction and IL-10 is required to restrain pduC-dependent dextran sodium sulfate (DSS)-induced colitis. Using a catalytically-inactive mutant, we determined that PduC metabolic activity was required for this immune phenotype. Cell-free supernatants from WT AIEC (but not the isogenic, pduC-deficient clone) promoted ex vivo Th17 cell polarization and metabolomics analysis (LC-MS) of these supernatants defined PduC-dependent metabolites capable of promoting Th17 polarization. These studies reveal a link between AIEC microbial metabolism and inflammatory Th17 cells with the potential to serve as a therapeutic target in the treatment of Crohn’s disease.

scholarly journals Does COVID-19 Affect Adult Neurogenesis? A Neurochemical Perspective

2021 ◽  
Author(s):  
Jayakumar Saikarthik ◽  
Ilango Saraswathi ◽  
Abdulrahman A. Al-Atram
Keyword(s):  
Adult Neurogenesis ◽  
Cell Activation ◽  
Immune Cell ◽  
Neuropsychiatric Symptoms ◽  
Brain Regions ◽  
Immune Cell Activation ◽  
Brain Involvement ◽  
The Impact ◽  
The Brain

COVID-19 has been found to cause neuropsychiatric symptoms which indicate brain involvement. SARS-CoV-2 may enter the brain by damaging and penetrating olfactory mucosa and via other possible routes like damaged blood–brain barrier, and hematologic spread. With SARS-CoV-2 having a higher affinity to ACE2 receptors, brain regions that have higher ACE2 receptors like the hippocampus, are more vulnerable to the effect of the viral invasion. In addition, immune cell activation, an important feature of COVID-19, leads to cytokine storm which causes neurotoxicity, neuroinflammation, and neurodegeneration. Impaired adult neurogenesis is related to many psychiatric disorders including depression, bipolar disorder, anxiety disorder, schizophrenia, and PTSD. It is known to be related to the depletion of neurotransmitters, dopamine, serotonin, norepinephrine, GABA, and glutamate which play a major role in adult neurogenesis. A recent study reveals that SSRI which acts by increasing serotonin is proven beneficial in COVID-19 patients. Thus, the current chapter will discuss the impact of COVID-19 on adult neurogenesis with emphasis on the role of ACE2 and neurotransmitters.

scholarly journals Immunotherapy Summary for Cytokine Storm in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Yaqun Li ◽  
Wenjie Zhao ◽  
Jinhua Liu ◽  
Zichao Chen ◽  
Qingtao Lv ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cell Activation ◽  
Immune Cell ◽  
Effective Means ◽  
Clinical Effectiveness ◽  
The Body ◽  
Cytokine Storm ◽  
Immune Cell Activation ◽  
Novel Coronavirus ◽  
Immune Imbalance

COVID-19 pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ravaged the world, resulting in an alarming number of infections and deaths, and the number continues to increase. The pathogenesis caused by the novel coronavirus was found to be a disruption of the pro-inflammatory/anti-inflammatory response. Due to the lack of effective treatments, different strategies and treatment methods are still being researched, with the use of vaccines to make the body immune becoming the most effective means of prevention. Antiviral drugs and respiratory support are often used clinically as needed, but are not yet sufficient to alleviate the cytokine storm (CS) and systemic inflammatory response syndrome. How to neutralize the cytokine storm and inhibit excessive immune cell activation becomes the key to treating neocoronavirus pneumonia. Immunotherapy through the application of hormones and monoclonal antibodies can alleviate the immune imbalance, but the clinical effectiveness and side effects remain controversial. This article reviews the pathogenesis of neocoronavirus pneumonia and discusses the immunomodulatory therapies currently applied to COVID-19. We aim to give some conceptual thought to the prevention and immunotherapy of neocoronavirus pneumonia.

scholarly journals Pyroptosis at the forefront of anticancer immunity

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Reid Loveless ◽  
Ryan Bloomquist ◽  
Yong Teng
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Tumor Regression ◽  
Tumor Resistance ◽  
Immune Cell Activation ◽  
Cell Death Pathway ◽  
Immunosuppressive Tumor Microenvironment ◽  
Cancer Intervention ◽  
The Impact ◽  
Anticancer Immunity

AbstractTumor resistance to apoptosis and the immunosuppressive tumor microenvironment are two major contributors to poor therapeutic responses during cancer intervention. Pyroptosis, a lytic and inflammatory programmed cell death pathway distinct from apoptosis, has subsequently sparked notable interest among cancer researchers for its potential to be clinically harnessed and to address these problems. Recent evidence indicates that pyroptosis induction in tumor cells leads to a robust inflammatory response and marked tumor regression. Underlying its antitumor effect, pyroptosis is mediated by pore-forming gasdermin proteins that facilitate immune cell activation and infiltration through their release of pro-inflammatory cytokines and immunogenic material following cell rupture. Considering its inflammatory nature, however, aberrant pyroptosis may also be implicated in the formation of a tumor supportive microenvironment, as evidenced by the upregulation of gasdermin proteins in certain cancers. In this review, the molecular pathways leading to pyroptosis are introduced, followed by an overview of the seemingly entangled links between pyroptosis and cancer. We describe what is known regarding the impact of pyroptosis on anticancer immunity and give insight into the potential of harnessing pyroptosis as a tool and applying it to novel or existing anticancer strategies.

scholarly journals Exploiting aneuploidy-imposed stresses and coping mechanisms to battle cancer

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200148
Author(s):  
Lin Zhou ◽  
Laura J. Jilderda ◽  
Floris Foijer
Keyword(s):  
Cancer Cells ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Metabolic Stress ◽  
Coping Mechanisms ◽  
Immune Cell Activation ◽  
Cycle Arrest ◽  
Biological Responses ◽  
And Coping

Aneuploidy, an irregular number of chromosomes in cells, is a hallmark feature of cancer. Aneuploidy results from chromosomal instability (CIN) and occurs in almost 90% of all tumours. While many cancers display an ongoing CIN phenotype, cells can also be aneuploid without displaying CIN. CIN drives tumour evolution as ongoing chromosomal missegregation will yield a progeny of cells with variable aneuploid karyotypes. The resulting aneuploidy is initially toxic to cells because it leads to proteotoxic and metabolic stress, cell cycle arrest, cell death, immune cell activation and further genomic instability. In order to overcome these aneuploidy-imposed stresses and adopt a malignant fate, aneuploid cancer cells must develop aneuploidy-tolerating mechanisms to cope with CIN. Aneuploidy-coping mechanisms can thus be considered as promising therapeutic targets. However, before such therapies can make it into the clinic, we first need to better understand the molecular mechanisms that are activated upon aneuploidization and the coping mechanisms that are selected for in aneuploid cancer cells. In this review, we discuss the key biological responses to aneuploidization, some of the recently uncovered aneuploidy-coping mechanisms and some strategies to exploit these in cancer therapy.

scholarly journals Disruption of MyD88 signaling suppresses hemophagocytic lymphohistiocytosis in mice

Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6582-6588 ◽  
Author(s):  
Philippe Krebs ◽  
Karine Crozat ◽  
Daniel Popkin ◽  
Michael B. Oldstone ◽  
Bruce Beutler
Keyword(s):  
T Cells ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Elevated Serum ◽  
Cytokine Signaling ◽  
Cell Contact ◽  
Inflammatory Disorder ◽  
Immune Cell Activation

AbstractHemophagocytic lymphohistiocytosis (HLH) is a rare inflammatory disorder with a poor prognosis for affected individuals. To find a means of suppressing the clinical phenotype, we investigated the cellular and molecular mechanisms leading to HLH in Unc13djinx/jinx mice, in which cytolytic function of NK and CD8+ T cells is impaired. Unc13djinx/jinx mutants infected with lymphochoriomeningitis virus (LCMV) present typical clinical features of HLH, including splenomegaly, elevated serum IFNγ, and anemia. Proteins mediating cell-cell contact, cytokine signaling or Toll-like receptor (TLR) signaling were analyzed. We show that neither the integrin CD18, which is involved in adhesion between antigen-presenting cells and effector T cells, nor tumor necrosis factor (TNF) made nonredundant contributions to the disease phenotype. Disruption of IFNγ signaling reduced immune cell activation in Unc13djinx/jinx mice, but also resulted in uncontrolled viral proliferation and exaggerated release of inflammatory cytokines. Abrogating the function of myeloid differentiation primary response gene 88 (MyD88) in Unc13djinx/jinx mice suppressed immune cell activation and controlled cytokine production in an IL-1 receptor 1 (IL-1R1)–independent way. Our findings implicate MyD88 as the key initiator of myeloid and lymphoid proliferation in HLH, and suggest that blockade of this signaling molecule may reduce immunopathology in patients.

scholarly journals Neuroinflammatory Basis of Depression: Learning From Experimental Models

2021 ◽  
Vol 15 ◽  
Author(s):  
Ruqayya Afridi ◽  
Kyoungho Suk
Keyword(s):  
Cell Activation ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Brain Regions ◽  
Experimental Models ◽  
Sterile Inflammation ◽  
Immune Cell Activation ◽  
Glial Cell Activation ◽  
Intensive Investigation

The neuroinflammatory basis of depression encompasses the detrimental role of otherwise supportive non-neuronal cells and neuroinflammation in hampering neuronal function, leading to depressive behavior. Animals subjected to different stress paradigms show glial cell activation and a surge in proinflammatory cytokines in various brain regions. The concept of sterile inflammation observed in animal models of depression has intrigued many researchers to determine the possible triggers of central immune cell activation. Notably, microglial activation and subsequent phenotypic polarization in depression have been strongly advocated by the wealth of recent preclinical studies; however, findings from human studies have shown contradictory results. Despite intensive investigation, many research gaps still exist to elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression. In this mini-review, recent progress in understanding neuroinflammatory mechanisms in light of experimental models of depression will be thoroughly discussed. The challenges of mirroring depression in animal and in vitro models will also be highlighted. Furthermore, prospects of targeting neuroinflammation to treat depressive disorder will be covered.

Oxidized Haemoglobin–Driven Endothelial Dysfunction and Immune Cell Activation: Novel Therapeutic Targets for Atherosclerosis

2013 ◽  
Vol 20 (37) ◽  
pp. 4806-4814 ◽  
Author(s):  
Brigitta Buttari ◽  
Elisabetta Profumo ◽  
Rita Businaro ◽  
Luciano Saso ◽  
Raffaele Capoano ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Cell Activation ◽  
Immune Cell ◽  
Therapeutic Targets ◽  
Immune Cell Activation ◽  
Novel Therapeutic

scholarly journals Neuronal guidance proteins in cardiovascular inflammation

2021 ◽  
Vol 116 (1) ◽  
Author(s):  
Marius Keller ◽  
Valbona Mirakaj ◽  
Michael Koeppen ◽  
Peter Rosenberger
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Vascular Endothelial ◽  
Therapeutic Approaches ◽  
Immune Cell Activation ◽  
Cytokines And Chemokines ◽  
The Future ◽  
Cardiovascular Pathologies ◽  
Neuronal Guidance

AbstractCardiovascular pathologies are often induced by inflammation. The associated changes in the inflammatory response influence vascular endothelial biology; they complicate the extent of ischaemia and reperfusion injury, direct the migration of immune competent cells and activate platelets. The initiation and progression of inflammation is regulated by the classical paradigm through the system of cytokines and chemokines. Therapeutic approaches have previously used this knowledge to control the extent of cardiovascular changes with varying degrees of success. Neuronal guidance proteins (NGPs) have emerged in recent years and have been shown to be significantly involved in the control of tissue inflammation and the mechanisms of immune cell activation. Therefore, proteins of this class might be used in the future as targets to control the extent of inflammation in the cardiovascular system. In this review, we describe the role of NGPs during cardiovascular inflammation and highlight potential therapeutic options that could be explored in the future.

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