scholarly journals Targeting Mononuclear Phagocyte Receptors in Cancer Immunotherapy: New Perspectives of the Triggering Receptor Expressed on Myeloid Cells (TREM-1)

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1337
Author(s):  
Federica Raggi ◽  
Maria Bosco
Keyword(s):  
Tumor Progression ◽  
Cancer Immunotherapy ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Therapeutic Strategies ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Receptor Expression ◽  
Tumor Phenotype

Inflammatory cells are major players in the onset of cancer. The degree of inflammation and type of inflammatory cells in the tumor microenvironment (TME) are responsible for tilting the balance between tumor progression and regression. Cancer-related inflammation has also been shown to influence the efficacy of conventional therapy. Mononuclear phagocytes (MPs) represent a major component of the inflammatory circuit that promotes tumor progression. Despite their potential to activate immunosurveillance and exert anti-tumor responses, MPs are subverted by the tumor to support its growth, immune evasion, and spread. MP responses in the TME are dictated by a network of stimuli integrated through the cross-talk between activatory and inhibitory receptors. Alterations in receptor expression/signaling can create excessive inflammation and, when chronic, promote tumorigenesis. Research advances have led to the development of new therapeutic strategies aimed at receptor targeting to induce a tumor-infiltrating MP switch from a cancer-supportive toward an anti-tumor phenotype, demonstrating efficacy in different human cancers. This review provides an overview of the role of MP receptors in inflammation-mediated carcinogenesis and discusses the most recent updates regarding their targeting for immunotherapeutic purposes. We focus in particular on the TREM-1 receptor, a major amplifier of MP inflammatory responses, highlighting its relevance in the development and progression of several types of inflammation-associated malignancies and the promises of its inhibition for cancer immunotherapy.

scholarly journals Modulation of Macrophages M1/M2 Polarization Using Carbohydrate-Functionalized Polymeric Nanoparticles

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 88
Author(s):  
Raquel G. D. Andrade ◽  
Bruno Reis ◽  
Benjamin Costas ◽  
Sofia A. Costa Lima ◽  
Salette Reis
Keyword(s):  
Inflammatory Responses ◽  
Polymeric Nanoparticles ◽  
Interaction Mechanism ◽  
Mannose Receptor ◽  
The Body ◽  
Receptor Expression ◽  
Production Methods ◽  
Polymeric Nanocarriers ◽  
Efficient Delivery

Exploiting surface endocytosis receptors using carbohydrate-conjugated nanocarriers brings outstanding approaches to an efficient delivery towards a specific target. Macrophages are cells of innate immunity found throughout the body. Plasticity of macrophages is evidenced by alterations in phenotypic polarization in response to stimuli, and is associated with changes in effector molecules, receptor expression, and cytokine profile. M1-polarized macrophages are involved in pro-inflammatory responses while M2 macrophages are capable of anti-inflammatory response and tissue repair. Modulation of macrophages’ activation state is an effective approach for several disease therapies, mediated by carbohydrate-coated nanocarriers. In this review, polymeric nanocarriers targeting macrophages are described in terms of production methods and conjugation strategies, highlighting the role of mannose receptor in the polarization of macrophages, and targeting approaches for infectious diseases, cancer immunotherapy, and prevention. Translation of this nanomedicine approach still requires further elucidation of the interaction mechanism between nanocarriers and macrophages towards clinical applications.

scholarly journals Monosodium Urate Microcrystals Induce Cyclooxygenase-2 in Human Monocytes

Blood ◽  
1998 ◽  
Vol 91 (5) ◽  
pp. 1769-1776 ◽  
Author(s):  
Marc Pouliot ◽  
Michael J. James ◽  
Shaun R. McColl ◽  
Paul H. Naccache ◽  
Leslie G. Cleland
Keyword(s):  
De Novo ◽  
Inflammatory Responses ◽  
Gouty Arthritis ◽  
Calcium Pyrophosphate ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Mitogen Activated Protein Kinase ◽  
Calcium Pyrophosphate Dihydrate ◽  
Monosodium Urate ◽  
Cox 2

Abstract The formation and deposition of monosodium urate (MSU) microcrystals in articular and periarticular tissues is the causative agent of acute or chronic inflammatory responses known as gouty arthritis. Mononuclear phagocyte activation is involved in early triggering events of gout attacks. Because stimulated mononuclear phagocytes can constitute an important source of the inducible isoform of cyclooxygenase (COX-2), we evaluated the effects that proinflammatory microcrystals might have on COX-2 protein expression in crystal-stimulated monocytes. We found that MSU crystals, but not calcium pyrophosphate dihydrate (CPPD) crystals, induced COX-2, which correlated with the synthesis of prostaglandin E2 (PGE2) and thromboxane A2(TXA2). Crystal-induced de novo synthesis of COX-2 was dependent on transcriptional and translational events. Inhibition of tyrosine phosphorylation, by herbimycin A, blocked crystal-induced COX-2. Similarly, an inhibitor of the p38 mitogen-activated protein kinase, SB 203580, inhibited the stimulation of COX-2. Colchicine inhibited crystal-induced COX-2. In all cases, prostanoid synthesis was concomitantly inhibited. Taken together, these results implicate COX-2 in the development of MSU-induced inflammation.

Immunoregulation through extracellular nucleotides

Blood ◽  
2012 ◽  
Vol 120 (3) ◽  
pp. 511-518 ◽  
Author(s):  
Laura Vitiello ◽  
Stefania Gorini ◽  
Giuseppe Rosano ◽  
Andrea la Sala
Keyword(s):  
Inflammatory Responses ◽  
Receptor Expression ◽  
Extracellular Nucleotides ◽  
P2 Receptor ◽  
Murine Models ◽  
Danger Signal ◽  
Chronic Stimulation ◽  
P2 Purinergic Receptors ◽  
Human Immune

Abstract Extracellular ATP (eATP), the most abundant among nucleotides, can act as a mediator during inflammatory responses by binding to plasmamembrane P2 purinergic receptors, which are widely expressed on cells of the immune system. eATP is generally considered as a classical danger signal, which stimulates immune responses in the presence of tissue damage. Converging evidence from several studies using murine models of chronic inflammation have supported this hypothesis; however, the role of eATP in the regulation of human immune function appears to be more complex. Chronic stimulation with micromolar eATP concentrations inhibits the proliferation of T and NK lymphocytes and enhances the capacity of dendritic cells to promote tolerance. The effect of eATP depends on multiple factors, such as the extent of stimulation, eATP concentration, presence/absence of other mediators in the microenvironment, and pattern of P2 receptor engagement. Small but significant differences in the pattern of P2 receptor expression in mice and humans confer the diverse capacities of ATP in regulating the immune response. Such diversity, which is often overlooked, should therefore be carefully considered when evaluating the role of eATP in human inflammatory and autoimmune diseases.

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 Airways inflammatory and atopy-related responses in athletes

2009 ◽  
Vol 18 (2) ◽  
pp. 46 ◽  
Author(s):  
AJ McKune ◽  
LL Smith
Keyword(s):  
South African ◽  
Sports Medicine ◽  
Inflammatory Responses ◽  
Cell Damage ◽  
Inflammatory Cells ◽  
Endurance Athletes ◽  
Airway Trauma ◽  
Airway Symptoms ◽  
Cytokine Milieu

The prevalence of asthma and airway hyperresponsiveness (AHR) in highly trained endurance athletes is rising. The type of training (i.e. endurance, or speed and power) seems to influence the airway symptoms. High-intensity exercise and training might contribute to the development of asthma or AHR in athletes previously unaffected by these airway disorders. Repeated hyperventilation of unconditioned air, as well as air containing irritants and/or allergens has been suggested to cause thermal, mechanical, or osmotic airway trauma resulting in damage to the airway epithelium. Subsequent airway inflammatory responses may be responsible for the development of atopy-related symptoms in endurance athletes such as those observed in asthma and AHR. Eosinophils and neutrophils are the inflammatory cells that have been frequently observed to be elevated in the airways of endurance athletes. The trafficking of these cells to the airways may possibly be regulated by TH2 cytokines that are expressed in the airways in response to epithelial cell damage. In addition, these airway inflammatory responses may lead to airway remodelling similar to that which occurs in asthma. The effect of the exercise challenge itself may initiate airway atopy-related and inflammatory responses in endurance athletes. While the literature seems to support the role of local airway conditions and/or events in inducing atopy-related symptoms in athletes, it is proposed that alterations in the hormonal and/or cytokine milieu with intense competition and/or training may also play a role. South African Journal of Sports Medicine Vol. 18 (2) 2006: pp. 46-51

scholarly journals Fibronectin in Cancer: Friend or Foe

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 27 ◽  
Author(s):  
Tsung-Cheng Lin ◽  
Cheng-Han Yang ◽  
Li-Hsin Cheng ◽  
Wen-Tsan Chang ◽  
Yuh-Rong Lin ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Poor Prognosis ◽  
Therapeutic Strategies ◽  
Malignant Progression ◽  
Metastatic Progression ◽  
Future Perspectives ◽  
Tumor Microenvironments ◽  
Tumor Transformation

The role of fibronectin (FN) in tumorigenesis and malignant progression has been highly controversial. Cancerous FN plays a tumor-suppressive role, whereas it is pro-metastatic and associated with poor prognosis. Interestingly, FN matrix deposited in the tumor microenvironments (TMEs) promotes tumor progression but is paradoxically related to a better prognosis. Here, we justify how FN impacts tumor transformation and subsequently metastatic progression. Next, we try to reconcile and rationalize the seemingly conflicting roles of FN in cancer and TMEs. Finally, we propose future perspectives for potential FN-based therapeutic strategies.

scholarly journals Leishmania Infection Impairs β1-Integrin Function and Chemokine Receptor Expression in Mononuclear Phagocytes

2006 ◽  
Vol 74 (7) ◽  
pp. 3912-3921 ◽  
Author(s):  
Nathanael F. Pinheiro ◽  
Micely D. R. Hermida ◽  
Mariana P. Macedo ◽  
José Mengel ◽  
Andre Bafica ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Connective Tissue ◽  
Chemokine Receptors ◽  
Parasite Burden ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Receptor Expression ◽  
Leishmania Infection ◽  
Intracellular Parasites ◽  
Macrophage Adhesion

ABSTRACT Leishmania spp. are intracellular parasites that cause lesions in the skin, mucosa, and viscera. We have previously shown that Leishmania infection reduces mononuclear phagocyte adhesion to inflamed connective tissue. In this study, we examined the role of adhesion molecules and chemokines in this process. Infection rate (r = −0.826, P = 0.003) and parasite burden (r = −0.917, P = 0.028) negatively correlated to mouse phagocyte adhesion. The decrease (58.7 to 75.0% inhibition, P = 0.005) in phagocyte adhesion to connective tissue, induced by Leishmania, occurred as early as 2 h after infection and was maintained for at least 24 h. Interestingly, impairment of cell adhesion was sustained by phagocyte infection, since it was not observed following phagocytosis of killed parasites (cell adhesion varied from 15.2% below to 24.0% above control levels, P > 0.05). In addition, Leishmania infection diminished cell adhesion to fibronectin (54.1 to 96.2%, P < 0.01), collagen (15.7 to 83.7%, P < 0.05), and laminin (59.1 to 82.2%, P < 0.05). The CD11bhi subpopulation was highly infected (49.6 to 97.3%). Calcium and Mg2+ replacement by Mn2+, a treatment that is known to induce integrins to a high state of affinity for their receptors, reverted the inhibition in adhesion caused by Leishmania. This reversion was completely blocked by anti-VLA4 antibodies. Furthermore, expression of CCR4 and CCR5, two chemokine receptors implicated in cell adhesion, was found to be downregulated 16 h after infection (2.8 to 4.1 times and 1.9 to 2.8 times, respectively). Together, these results suggest that mechanisms regulating integrin function are implicated in the change of macrophage adhesion in leishmaniasis.

scholarly journals The Immunobiology of Prostanoid Receptor Signaling in Connecting Innate and Adaptive Immunity

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Hedi Harizi
Keyword(s):  
Adaptive Immunity ◽  
Inflammatory Cells ◽  
Cell Interaction ◽  
Membrane Receptors ◽  
Receptor Expression ◽  
Receptor Signaling ◽  
Cell Surface Molecule ◽  
Innate And Adaptive Immunity ◽  
Prostanoid Receptor

Prostanoids, including prostaglandins (PGs), thromboxanes (TXs), and prostacyclins, are synthesized from arachidonic acid (AA) by the action of Cyclooxygenase (COX) enzymes. They are bioactive inflammatory lipid mediators that play a key role in immunity and immunopathology. Prostanoids exert their effects on immune and inflammatory cells by binding to membrane receptors that are widely expressed throughout the immune system and act at multiple levels in innate and adaptive immunity. The immunoregulatory role of prostanoids results from their ability to regulate cell-cell interaction, antigen presentation, cytokine production, cytokine receptor expression, differentiation, survival, apoptosis, cell-surface molecule levels, and cell migration in both autocrine and paracrine manners. By acting on immune cells of both systems, prostanoids and their receptors have great impact on immune regulation and play a pivotal role in connecting innate and adaptive immunity. This paper focuses on the immunobiology of prostanoid receptor signaling because of their potential clinical relevance for various disorders including inflammation, autoimmunity, and tumorigenesis. We mainly discuss the effects of major COX metabolites, PGD2, PGE2, their signaling during dendritic cell (DC)-natural killer (NK) reciprocal crosstalk, DC-T cell interaction, and subsequent consequences on determining crucial aspects of innate and adaptive immunity in normal and pathological settings.

scholarly journals The Adipokine Network in Rheumatic Joint Diseases

2019 ◽  
Vol 20 (17) ◽  
pp. 4091 ◽  
Author(s):  
Mar Carrión ◽  
Klaus W. Frommer ◽  
Selene Pérez-García ◽  
Ulf Müller-Ladner ◽  
Rosa P. Gomariz ◽  
...  
Keyword(s):  
Rheumatic Diseases ◽  
Inflammatory Responses ◽  
Functional Limitations ◽  
Inflammatory Cells ◽  
Signal Molecules ◽  
Lipocalin 2 ◽  
Effector Cells ◽  
Bidirectional Communication ◽  
Rheumatic Conditions

Rheumatic diseases encompass a diverse group of chronic disorders that commonly affect musculoskeletal structures. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common, leading to considerable functional limitations and irreversible disability when patients are unsuccessfully treated. Although the specific causes of many rheumatic conditions remain unknown, it is generally accepted that immune mechanisms and/or uncontrolled inflammatory responses are involved in their etiology and symptomatology. In this regard, the bidirectional communication between neuroendocrine and immune system has been demonstrated to provide a homeostatic network that is involved in several pathological conditions. Adipokines represent a wide variety of bioactive, immune and inflammatory mediators mainly released by adipocytes that act as signal molecules in the neuroendocrine-immune interactions. Adipokines can also be synthesized by synoviocytes, osteoclasts, osteoblasts, chondrocytes and inflammatory cells in the joint microenvironment, showing potent modulatory properties on different effector cells in OA and RA pathogenesis. Effects of adiponectin, leptin, resistin and visfatin on local and systemic inflammation are broadly described. However, more recently, other adipokines, such as progranulin, chemerin, lipocalin-2, vaspin, omentin-1 and nesfatin, have been recognized to display immunomodulatory actions in rheumatic diseases. This review highlights the latest relevant findings on the role of the adipokine network in the pathophysiology of OA and RA.

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