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

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms20030676 ◽

2019 ◽

Vol 20 (3) ◽

pp. 676 ◽

Cited By ~ 29

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.

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Neuroinflammation in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia and the Interest of Induced Pluripotent Stem Cells to Study Immune Cells Interactions With Neurons

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.767041 ◽

2021 ◽

Vol 14 ◽

Author(s):

Elise Liu ◽

Léa Karpf ◽

Delphine Bohl

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Immune System ◽

Frontotemporal Dementia ◽

Immune Cells ◽

Immune Cell ◽

Current Knowledge ◽

Cell Types ◽

Induced Pluripotent ◽

Different Cell Types ◽

Lateral Sclerosis

Inflammation is a shared hallmark between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). For long, studies were conducted on tissues of post-mortem patients and neuroinflammation was thought to be only bystander result of the disease with the immune system reacting to dying neurons. In the last two decades, thanks to improving technologies, the identification of causal genes and the development of new tools and models, the involvement of inflammation has emerged as a potential driver of the diseases and evolved as a new area of intense research. In this review, we present the current knowledge about neuroinflammation in ALS, ALS-FTD, and FTD patients and animal models and we discuss reasons of failures linked to therapeutic trials with immunomodulator drugs. Then we present the induced pluripotent stem cell (iPSC) technology and its interest as a new tool to have a better immunopathological comprehension of both diseases in a human context. The iPSC technology giving the unique opportunity to study cells across differentiation and maturation times, brings the hope to shed light on the different mechanisms linking neurodegeneration and activation of the immune system. Protocols available to differentiate iPSC into different immune cell types are presented. Finally, we discuss the interest in studying monocultures of iPS-derived immune cells, co-cultures with neurons and 3D cultures with different cell types, as more integrated cellular approaches. The hope is that the future work with human iPS-derived cells helps not only to identify disease-specific defects in the different cell types but also to decipher the synergistic effects between neurons and immune cells. These new cellular tools could help to find new therapeutic approaches for all patients with ALS, ALS-FTD, and FTD.

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Implications of microRNAs in the pathogenesis of atherosclerosis and prospects for therapy

Current Drug Targets ◽

10.2174/1389450122666210120143450 ◽

2021 ◽

Vol 22 ◽

Author(s):

Armita Mahdavi Gorabi ◽

Mohsen Ghanbari ◽

Thozhukat Sathyapalan ◽

Tannaz Jamialahmadi ◽

Amirhossein Sahebkar

Keyword(s):

Immune Cell ◽

Cholesterol Metabolism ◽

Current Knowledge ◽

Inflammatory Cells ◽

Cell Types ◽

Fine Tuning ◽

Lipid Uptake ◽

Atherosclerosis Development ◽

Signaling Receptors ◽

Different Cell Types

MicroRNAs (miRNAs) are non-coding RNAs containing around 22 nucleotides, which are expressed in vertebrates and plants. They act as posttranscriptional gene expression regulators, fine-tuning various biological processes in different cell types. There is emerging evidence on their role in different stages of atherosclerosis. In addition to regulating the inflammatory cells involved in atherosclerosis, miRNAs play fundamental roles in the pathophysiology of atherosclerosis such as endothelial cell (EC) dysfunction, the aberrant function of the vascular smooth muscle cell (VSMC) and cholesterol metabolism. Moreover, miRNAs participate in several pathogenic pathways of atherosclerotic plaque development, including their effects on immune cell signaling receptors and lipid uptake. In this study, we review our current knowledge of the regulatory role of miRNAs in various pathogenic pathways underlying atherosclerosis development and also outline potential clinical applications of miRNAs in atherosclerosis.

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Neutrophils as Orchestrators in Tumor Development and Metastasis Formation

Frontiers in Oncology ◽

10.3389/fonc.2020.581457 ◽

2020 ◽

Vol 10 ◽

Author(s):

Lydia Kalafati ◽

Ioannis Mitroulis ◽

Panayotis Verginis ◽

Triantafyllos Chavakis ◽

Ioannis Kourtzelis

Keyword(s):

Immune Cell ◽

Current Knowledge ◽

Tumor Development ◽

Metastasis Formation ◽

Cell Plasticity ◽

Inhibit Tumor Growth ◽

Therapeutic Modalities ◽

Mediated Effects ◽

Immune Cell Subsets ◽

Metastasis Development

Several lines of clinical and experimental evidence suggest that immune cell plasticity is a central player in tumorigenesis, tumor progression, and metastasis formation. Neutrophils are able to promote or inhibit tumor growth. Through their interaction with tumor cells or their crosstalk with other immune cell subsets in the tumor microenvironment, they modulate tumor cell survival. Here, we summarize current knowledge with regards to the mechanisms that underlie neutrophil–mediated effects on tumor establishment and metastasis development. We also discuss the tumor-mediated effects on granulopoiesis and neutrophil precursors in the bone marrow and the involvement of neutrophils in anti-tumor therapeutic modalities.

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Regulatory T Cell Development

Annual Review of Immunology ◽

10.1146/annurev-immunol-100219-020937 ◽

2020 ◽

Vol 38 (1) ◽

pp. 421-453 ◽

Cited By ~ 10

Author(s):

Peter A. Savage ◽

David E.J. Klawon ◽

Christine H. Miller

Keyword(s):

Treg Cell ◽

Current Knowledge ◽

T Cell Development ◽

Cell Types ◽

Treg Cells ◽

Cell Development ◽

Clear Understanding ◽

Major Barrier ◽

Health And Disease ◽

Antigen Presenting

Foxp3-expressing CD4+ regulatory T (Treg) cells play key roles in the prevention of autoimmunity and the maintenance of immune homeostasis and represent a major barrier to the induction of robust antitumor immune responses. Thus, a clear understanding of the mechanisms coordinating Treg cell differentiation is crucial for understanding numerous facets of health and disease and for developing approaches to modulate Treg cells for clinical benefit. Here, we discuss current knowledge of the signals that coordinate Treg cell development, the antigen-presenting cell types that direct Treg cell selection, and the nature of endogenous Treg cell ligands, focusing on evidence from studies in mice. We also highlight recent advances in this area and identify key unanswered questions.

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

ISRN Inflammation ◽

10.1155/2013/139239 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 385

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.

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The Immune System of Mesothelioma Patients: A Window of Opportunity for Novel Immunotherapies

10.5772/intechopen.98617 ◽

2021 ◽

Author(s):

Fabio Nicolini ◽

Massimiliano Mazza

Keyword(s):

Immune System ◽

Immune Cells ◽

Immune Cell ◽

Current Knowledge ◽

Cell Types ◽

Screening Strategies ◽

Tertiary Lymphoid Structures ◽

Lymphoid Structures ◽

Review Current

The interplay between the immune system and the pleural mesothelium is crucial both for the development of malignant pleural mesothelioma (MPM) and for the response of MPM patients to therapy. MPM is heavily infiltrated by several immune cell types which affect the progression of the disease. The presence of organized tertiary lymphoid structures (TLSs) witness the attempt to fight the disease in situ by adaptive immunity which is often suppressed by tumor expressed factors. In rare patients physiological, pharmacological or vaccine-induced immune response is efficient, rendering their plasma a valuable resource of anti-tumor immune cells and molecules. Of particular interest are human antibodies targeting antigens at the tumor cell surface. Here we review current knowledge regarding MPM immune infiltration, MPM immunotherapy and the harnessing of this response to identify novel biologics as biomarkers and therapeutics through innovative screening strategies.

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The inflammatory cytokine, interleukin‐1‐beta, drives central immune cell infiltration, changes in sympathetic nerve activity and blood pressure

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.04682 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

Song Tieng Yao ◽

Alicia Lai Ting Chan ◽

Khalid Elsaafien ◽

Willian Seiji Korim

Keyword(s):

Blood Pressure ◽

Sympathetic Nerve ◽

Inflammatory Cytokine ◽

Sympathetic Nerve Activity ◽

Immune Cell ◽

Interleukin 1 ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Interleukin 1 Beta ◽

Nerve Activity

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Identification and characterization of human dendritic cell subsets in the steady state: a review of our current knowledge

Journal of Investigative Medicine ◽

10.1136/jim-2016-000072 ◽

2016 ◽

Vol 64 (4) ◽

pp. 833-847 ◽

Cited By ~ 10

Author(s):

Vineet Indrajit Patel ◽

Jordan Patrick Metcalf

Keyword(s):

Steady State ◽

Current Knowledge ◽

Cell Types ◽

Lymphoid Tissues ◽

Transcriptional Level ◽

Functional Abilities ◽

Tissue Samples ◽

To Come ◽

Antigen Presenting

Dendritic cells (DC) are generally categorized as a group of rare antigen presenting cells that are to the crucial development of immune responses to pathogens and also of tolerance to self-antigens. Therefore, having the ability to identify DC in specific tissues and to test their functional abilities in the steady state are scientific gaps needing attention. Research on primary human DC is lacking due to their rarity and the difficulty of obtaining tissue samples. However, recent findings have shown that several different DC subsets exist, and that these subsets vary both by markers expressed and functions depending on their specific microenvironment. After discriminating from other cell types, DC can be split into myeloid and plasmacytoid fractions. While plasmacytoid DC express definite markers, CD123 and BDCA-2, myeloid DC encompass several different subsets with overlapping markers expressed. Such markers include the blood DC antigens BDCA-1 and BDCA-3, along with Langerin, CD1a and CD14. Marker specificity is further reduced when accounting for microenvironmental differences, as observed in the blood, primary lymphoid tissues, skin and lungs. The mixed leukocyte reaction (MLR) has been used to measure the strength of antigen presentation by specific DC subsets. Surface markers and MLR require standardization to enable consistent identification of and comparisons between DC subsets. To alleviate these issues, researchers have begun comparing DC subsets at the transcriptional level. This has allowed degrees of relatedness to be determined between DC in different microenvironments, and should be a continued area of focus in years to come.

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