scholarly journals Inflammation and Pancreatic Cancer: Focus on Metabolism, Cytokines, and Immunity

2019 ◽  
Vol 20 (3) ◽  
pp. 676 ◽  
Author(s):  
Andrea Padoan ◽  
Mario Plebani ◽  
Daniela Basso
Keyword(s):  
Inflammatory Cell ◽  
Immune Cell ◽  
Suppressor Cells ◽  
Cell Types ◽  
Ductal Adenocarcinoma ◽  
Inflammatory Cell Infiltrate ◽  
Necrosis Factor Alpha ◽  
Relevant Role ◽  
Factor Alpha ◽  
Tumor Growth And Metastasis

Systemic and local chronic inflammation might enhance the risk of pancreatic ductal adenocarcinoma (PDAC), and PDAC-associated inflammatory infiltrate in the tumor microenvironment concurs in enhancing tumor growth and metastasis. Inflammation is closely correlated with immunity, the same immune cell populations contributing to both inflammation and immune response. In the PDAC microenvironment, the inflammatory cell infiltrate is unbalanced towards an immunosuppressive phenotype, with a prevalence of myeloid derived suppressor cells (MDSC), M2 polarized macrophages, and Treg, over M1 macrophages, dendritic cells, and effector CD4+ and CD8+ T lymphocytes. The dynamic and continuously evolving cross-talk between inflammatory and cancer cells might be direct and contact-dependent, but it is mainly mediated by soluble and exosomes-carried cytokines. Among these, tumor necrosis factor alpha (TNFα) plays a relevant role in enhancing cancer risk, cancer growth, and cancer-associated cachexia. In this review, we describe the inflammatory cell types, the cytokines, and the mechanisms underlying PDAC risk, growth, and progression, with particular attention on TNFα, also in the light of the potential risks or benefits associated with anti-TNFα treatments.

scholarly journals Interleukin-1 Beta—A Friend or Foe in Malignancies?

2018 ◽  
Vol 19 (8) ◽  
pp. 2155 ◽  
Author(s):  
Rebekka Bent ◽  
Lorna Moll ◽  
Stephan Grabbe ◽  
Matthias Bros
Keyword(s):  
Immune Cell ◽  
Current Knowledge ◽  
Interleukin 1 ◽  
Tumor Development ◽  
Suppressor Cells ◽  
Cell Types ◽  
Interleukin 1 Beta ◽  
Tumor Growth And Metastasis ◽  
Antigen Presenting ◽  
Th 1

Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial role in resolving acute inflammations, and by initiating adaptive anti-tumor responses. However, IL-1β generated in the course of chronic inflammation supports tumor development. Furthermore, IL-1β generated within the tumor microenvironment predominantly by tumor-infiltrating macrophages promotes tumor growth and metastasis via different mechanisms. These include the expression of IL-1 targets which promote neoangiogenesis and of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells. Moreover, IL-1 promotes the propagation of myeloid-derived suppressor cells. Using genetic mouse models as well as agents for pharmacological inhibition of IL-1 signaling therapeutically applied for treatment of IL-1 associated autoimmune diseases indicate that IL-1β is a driver of tumor induction and development.

scholarly journals Myeloid-Derived Suppressor Cells and Pancreatic Cancer: Implications in Novel Therapeutic Approaches

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1627 ◽  
Author(s):  
Anita Thyagarajan ◽  
Mamdouh Salman A. Alshehri ◽  
Kelly L.R. Miller ◽  
Catherine M. Sherwin ◽  
Jeffrey B. Travers ◽  
...  
Keyword(s):  
Survival Rates ◽  
Suppressor Cells ◽  
Cell Types ◽  
Therapeutic Agents ◽  
Ductal Adenocarcinoma ◽  
Cancer Therapies ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Resistance ◽  
Cellular Mechanisms ◽  
Immunosuppressive Cell

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating human malignancy with poor prognosis and low survival rates. Several cellular mechanisms have been linked with pancreatic carcinogenesis and also implicated in inducing tumor resistance to known therapeutic regimens. Of various factors, immune evasion mechanisms play critical roles in tumor progression and impeding the efficacy of cancer therapies including PDAC. Among immunosuppressive cell types, myeloid-derived suppressor cells (MDSCs) have been extensively studied and demonstrated to not only support PDAC development but also hamper the anti-tumor immune responses elicited by therapeutic agents. Notably, recent efforts have been directed in devising novel approaches to target MDSCs to limit their effects. Multiple strategies including immune-based approaches have been explored either alone or in combination with therapeutic agents to target MDSCs in preclinical and clinical settings of PDAC. The current review highlights the roles and mechanisms of MDSCs as well as the implications of this immunomodulatory cell type as a potential target to improve the efficacy of therapeutic regimens for PDAC.

The role of interleukins in the ovary

1996 ◽  
Vol 5 (1) ◽  
pp. 51-63 ◽  
Author(s):  
C Simón ◽  
A Tsafriri ◽  
A Pellicer ◽  
ML Polan
Keyword(s):  
Cell Types ◽  
Necrosis Factor Alpha ◽  
Communication Signals ◽  
Ability To Act ◽  
Tnf Α ◽  
History Of ◽  
Specific Antigens ◽  
Factor Alpha ◽  
Different Populations

A brief look at the history of cytokine research shows that the term ‘lymphokine’ was first described in 1969 as the product of sensitized lymphocytes exposed to specific antigens. To eliminate the incorrect notion that such proteins can be produced only by lymphocytes, Cohenet al.(1974) proposed the term ‘cytokines’ to indicate their production also by nonlymphoid cells.2After a long-persisting reluctance, it seems that ‘cytokine’ is becoming the prevalent term for these proteins. Meanwhile, a group of participants at the Second International Lymphokine Workshop held in 1979 proposed the term ‘interleukin’ in order to develop, ‘a system of nomenclature based on the protein's ability to act as communication signals between different populations of leukocytes’.3They introduced the names IL-I and IL-2 for two important cytokines. Since then the number of described interleukins reached 16 and this number may increase. Furthermore, notwithstanding this previous notion, interleukins are now known to be produced in a variety of tissues other than leucocytes and affect the functions of many and diverse somatic cell types (e.g. IL-1 or IL-6). Therefore, while many cytokines are now termed as interleukins, others continue to be known by their old names [e.g. tumour necrosis factor-alpha (TNF-α)], suggesting that they had been recognized earlier, but all of them are included under the generic name of cytokines.

scholarly journals Adipose Tissue in Obesity-Related Inflammation and Insulin Resistance: Cells, Cytokines, and Chemokines

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Kassem Makki ◽  
Philippe Froguel ◽  
Isabelle Wolowczuk
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Immune Cells ◽  
Metabolic Regulation ◽  
Immune Cell ◽  
Suppressor Cells ◽  
Cell Types ◽  
Immune Functions ◽  
Cytokines And Chemokines ◽  
Wide Range

Adipose tissue is a complex organ that comprises a wide range of cell types with diverse energy storage, metabolic regulation, and neuroendocrine and immune functions. Because it contains various immune cells, either adaptive (B and T lymphocytes; such as regulatory T cells) or innate (mostly macrophages and, more recently identified, myeloid-derived suppressor cells), the adipose tissue is now considered as a bona fide immune organ, at the cross-road between metabolism and immunity. Adipose tissue disorders, such as those encountered in obesity and lipodystrophy, cause alterations to adipose tissue distribution and function with broad effects on cytokine, chemokine, and hormone expression, on lipid storage, and on the composition of adipose-resident immune cell populations. The resulting changes appear to induce profound consequences for basal systemic inflammation and insulin sensitivity. The purpose of this review is to synthesize the current literature on adipose cell composition remodeling in obesity, which shows how adipose-resident immune cells regulate inflammation and insulin resistance—notably through cytokine and chemokine secretion—and highlights major research questions in the field.

Effects of Sulfur Mustard on Cytokines Released from Cultured Human Epidermal Keratinocytes

1998 ◽  
Vol 17 (3) ◽  
pp. 223-229 ◽  
Author(s):  
Elien M. Kurt ◽  
Robert J. Schafer ◽  
Carmen M. Arroyo
Keyword(s):  
Sulfur Mustard ◽  
Cell Types ◽  
Epidermal Keratinocytes ◽  
Cytokine Release ◽  
Experimental Conditions ◽  
Human Epidermal Keratinocytes ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Factor Alpha

The release of the cytokines interleukin (IL)-1α, IL-1β, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α was measured from epiderm alkeratinocytes in an attempt to characterize the immunologic response in keratinocytes following exposure to bis (2-chloroethyl)sulfide (sulfur mustard, HD). Enzyme-linked immunosorbentassay (ELISA) was used to measure cytokine levels in adult and neonatal culture human epidermal keratinocytes (HEK) 3 h after exposure to 0.50 and 1.0 m M HD. A two-way analysis of variance was carried out for cell type and HD concentration. That analysis showed significant differences between cell types for IL-1α and IL-1β(p =.001 and p =.015, respectively). In both of these cytokines, release in neonatal HEK decreased less than in adult HEK. A significant effectof HD concentration was shown only for IL-1β (P <.001), with cytokine release decreasing with increasing HD dose. In addition, a significant cell donor type by HD concentration interaction effect was found for IL-1β under the experimental conditions described in materials and methods. With increasing HD concentration, the relative decrease in cytokine release was much greater for adult than for neonatal HEK.

scholarly journals Mycobacterium tuberculosis Growth at theCavity Surface: a Microenvironment with FailedImmunity

2003 ◽  
Vol 71 (12) ◽  
pp. 7099-7108 ◽  
Author(s):  
Gilla Kaplan ◽  
Frank A. Post ◽  
Andre L. Moreira ◽  
Helen Wainwright ◽  
Barry N. Kreiswirth ◽  
...  
Keyword(s):  
Drug Resistance ◽  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cell Types ◽  
Cytokine Gene Expression ◽  
Cavity Surface ◽  
Activated T Cells ◽  
Necrosis Factor Alpha ◽  
Genetic Changes ◽  
Factor Alpha

ABSTRACT Protective immunity against pulmonary tuberculosis (TB) is characterized by the formation in the lungs of granulomas consisting of macrophages and activated T cells producing tumor necrosis factor alpha and gamma interferon, both required for the activation of the phagocytes. In 90% of immunocompetent humans, this response controls the infection. To understand why immunity fails in the other 10%, we studied the lungs of six patients who underwent surgery for incurable TB. Histologic examination of different lung lesions revealed heterogeneous morphology and distribution of acid-fast bacilli; only at the surface of cavities, i.e., in granulomas with a patent connection to the airways, were there numerous bacilli. The mutation profile of the isolates suggested that a single founder strain of Mycobacterium tuberculosis may undergo genetic changes during treatment, leading to acquisition of additional drug resistance independently in discrete physical locales. Additional drug resistance was preferentially observed at the cavity surface. Cytokine gene expression revealed that failure to control the bacilli was not associated with a generalized suppression of cellular immunity, since cytokine mRNA was up regulated in all lesions tested. Rather, a selective absence of CD4+ and CD8+ T cells was noted at the luminal surface of the cavity, preventing direct T-cell-macrophage interactions at this site, probably allowing luminal phagocytes to remain permissive for bacillary growth. In contrast, in the perinecrotic zone of the granulomas, the two cell types colocalized and bacillary numbers were substantially lower, suggesting that in this microenvironment an efficient bacteriostatic or bactericidal phagocyte population was generated.

scholarly journals THE INFLAMMATORY MICROENVIRONMENT IN SCREEN-DETECTED PREMALIGANT ADENOMATOUS POLYPS: EARLY RESULTS FROM THE INTEGRATED TECHNOLOGIES FOR IMPROVED POLYP SURVEILLANCE (INCISE) PROJECT

2020 ◽  
Author(s):  
David Mansouri ◽  
Stephen T McSorley ◽  
James H Park ◽  
Clare Orange ◽  
Paul G Horgan ◽  
...  
Keyword(s):  
Inflammatory Infiltrate ◽  
Inflammatory Cell ◽  
Immune Cell ◽  
Adenomatous Polyps ◽  
Cell Phenotype ◽  
Inflammatory Cell Infiltrate ◽  
Low Grade ◽  
Cell Infiltrate ◽  
Early Results ◽  
Significant Difference

Introduction Around 40% of patients who attend for colonoscopy following a positive stool screening test have adenomatous polyps. Identifying which patients have a higher propensity for malignant transformation is currently poorly understood. The aim of the present study was to assess whether the type and intensity of inflammatory infiltrate differs between high-grade (HGD) and low-grade dysplastic (LGD) screen detected adenomas. Methods A representative sample of 207 polyps from 134 individuals were included from a database of all patients with adenomas detected through the first round of the Scottish Bowel Screening Programme (SBoSP) in NHS GG&C (April 2009 to April 2011). Inflammatory cell phenotype infiltrate was assessed by immunohistochemistry for CD3+, CD8+, CD45+ and CD68+ in a semi-quantitative manner at 20x resolution. Immune-cell infiltrate was graded as absent, weak, moderate or strong. Patient and polyp characteristics and inflammatory infiltrate were then compared between HGD and LGD polyps. Results CD3+ infiltrate was significantly higher in HGD polyps compared to LGD polyps (74% vs 69%, p<0.05). CD8+ infiltrate was significantly higher in HGD polyps compared to LGD polyps (36% vs 13%, p<0.001) where as CD45+ infiltrate was not significantly different (69% vs 64%, p=0.401). There was no significant difference in CD68+ infiltrate (p=0.540) or total inflammatory cell infiltrate (calculated from CD3+ and CD68+) (p=0.226). Conclusions This study reports an increase in CD3+ and CD8+ infiltrate with progression from LGD to HGD in colonic adenomas. It may therefore have a use in the prognostic stratification and treatment of dysplastic polyps.

scholarly journals A Low Concentration of Ethanol Reduces the Chemiluminescence of Human Granulocytes and Monocytes but Not the Tumor Necrosis Factor Alpha Production by Monocytes after Endotoxin Stimulation

1998 ◽  
Vol 66 (6) ◽  
pp. 2809-2813 ◽  
Author(s):  
Alexandr Parlesak ◽  
Jens P. Diedrich ◽  
Christian Schäfer ◽  
Christiane Bode
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Cell Types ◽  
Polymorphonuclear Neutrophils ◽  
Alcohol Abusers ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT The ability of polymorphonuclear neutrophils (PMNs) and monocytes (Mφ) to produce reactive oxygen species (ROS) has been related closely to their potential in the killing of microorganisms. Ethanol has been shown to impair the generation of ROS in these phagocytes after stimulation with some immunogens and to increase the susceptibility of alcohol abusers to infectious diseases. As endotoxemia is common in alcohol abusers, we investigated the effect of ethanol (21.7 mmol/liter) on the luminol-amplified chemiluminescence of PMNs and Mφ after endotoxin stimulation and the release of tumor necrosis factor alpha (TNF-α) from Mφ. Further, the efficiency of ethanol to inactivate chemically generated ROS was tested. Significant stimulation of ROS release occurred at endotoxin concentrations of 1 ng/ml or higher in both PMNs and Mφ. Ethanol significantly suppressed the formation of ROS in both cell types, the decrease being more pronounced in Mφ (−73.8%) than in PMNs (−45.7%). The correlations between endotoxin concentration and the amount of released ROS showed a dose-dependent, sigmoidal course. Concentrations of endotoxin necessary for half-maximum stimulation were nearly identical (6 to 8 ng/ml) in both PMNs and Mφ, independent of the presence of ethanol. In contrast to ROS formation, ethanol had no effect on the amount of TNF-α produced by endotoxin-stimulated Mφ. Ethanol was shown to be unable to decrease the levels of chemically generated ROS under physiological conditions. Therefore, ethanol cannot be assumed to be an “antioxidative” compound but rather seems to modify processes of endotoxin recognition, intracellular signal transduction, or metabolism.

Fcγ receptor profile of monocytes and macrophages from rheumatoid arthritis patients and their response to immune complexes formed with autoantibodies to citrullinated proteins

2011 ◽  
Vol 70 (6) ◽  
pp. 1052-1059 ◽  
Author(s):  
Lætitia Laurent ◽  
Cyril Clavel ◽  
Olivia Lemaire ◽  
Florence Anquetil ◽  
Martin Cornillet ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Immune Complexes ◽  
Cell Types ◽  
Biological Data ◽  
Fcγ Receptor ◽  
Necrosis Factor Alpha ◽  
Monocytes And Macrophages ◽  
Citrullinated Proteins ◽  
Factor Alpha

ObjectiveTo analyse Fcγ receptor (FcγR) expression on monocytes and macrophages from rheumatoid arthritis (RA) patients versus healthy controls (HC), and to compare their responses to immune complexes containing RA-specific anti-citrullinated proteins auto antibodies (ACPA).MethodsMonocytes and monocyte-derived macrophages were obtained from the peripheral blood of 34 RA patients and 69 HC. FcγR expression was studied by flow cytometry. Cells were stimulated with ACPA-containing immune complexes, and tumour necrosis factor alpha (TNFα) was assayed in culture supernatants.ResultsVariations distinguished RA from HC monocytes, corresponding to a 5% and 6% decrease in the percentages of monocytes expressing FcγRI and FcγRII, respectively, and a 7% increase in the proportion of FcγRIII-positive monocytes. Although in both HC and RA patients macrophage differentiation was accompanied by a dramatic increase in the percentage of FcγRIII-expressing cells (72% vs 74.5%), the parallel decline in the proportion of FcγRI-positive cells was markedly smaller in RA (7% vs 43%). Monocytes and macrophages from patients were responsive to ACPA-containing immune complexes but TNFα production in both cell types neither differed from that observed with the corresponding cells from HC, nor correlated with FcγR expression or clinical or biological data. In RA as in HC, ACPA-containing immune complexes induced secretions of more TNFα in macrophages than in paired monocytes (ninefold). Finally, the proinflammatory potential of ACPA-containing immune complexes was confirmed in CD14-positive monocyte macrophages from the synovial fluid of four RA patients.ConclusionsACPA-containing immune complexes induce TNFα secretion by blood and synovial fluid-derived macrophages from RA patients, fitting with their probable involvement in RA pathophysiology.

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