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Journal of Experimental & Clinical... Dec 2023Myeloid cells (granulocytes and monocytes/macrophages) play an important role in neuroblastoma. By inducing a complex immunosuppressive network, myeloid cells pose a... (Review)
Review
Myeloid cells (granulocytes and monocytes/macrophages) play an important role in neuroblastoma. By inducing a complex immunosuppressive network, myeloid cells pose a challenge for the adaptive immune system to eliminate tumor cells, especially in high-risk neuroblastoma. This review first summarizes the pro- and anti-tumorigenic functions of myeloid cells, including granulocytes, monocytes, macrophages, and myeloid-derived suppressor cells (MDSC) during the development and progression of neuroblastoma. Secondly, we discuss how myeloid cells are engaged in the current treatment regimen and explore novel strategies to target these cells in neuroblastoma. These strategies include: (1) engaging myeloid cells as effector cells, (2) ablating myeloid cells or blocking the recruitment of myeloid cells to the tumor microenvironment and (3) reprogramming myeloid cells. Here we describe that despite their immunosuppressive traits, tumor-associated myeloid cells can still be engaged as effector cells, which is clear in anti-GD2 immunotherapy. However, their full potential is not yet reached, and myeloid cell engagement can be enhanced, for example by targeting the CD47/SIRPα axis. Though depletion of myeloid cells or blocking myeloid cell infiltration has been proven effective, this strategy also depletes possible effector cells for immunotherapy from the tumor microenvironment. Therefore, reprogramming of suppressive myeloid cells might be the optimal strategy, which reverses immunosuppressive traits, preserves myeloid cells as effectors of immunotherapy, and subsequently reactivates tumor-infiltrating T cells.
Topics: Humans; Neuroblastoma; Neoplasms; Myeloid Cells; Immunotherapy; Myeloid-Derived Suppressor Cells; Macrophages; Tumor Microenvironment
PubMed: 38087370
DOI: 10.1186/s13046-023-02913-9 -
Annual Review of Immunology Apr 2019Myeloid cells are a major cellular compartment of the immune system comprising monocytes, dendritic cells, tissue macrophages, and granulocytes. Models of cellular... (Review)
Review
Myeloid cells are a major cellular compartment of the immune system comprising monocytes, dendritic cells, tissue macrophages, and granulocytes. Models of cellular ontogeny, activation, differentiation, and tissue-specific functions of myeloid cells have been revisited during the last years with surprising results; for example, most tissue macrophages are yolk sac derived, monocytes and macrophages follow a multidimensional model of activation, and tissue signals have a significant impact on the functionality of all these cells. While these exciting results have brought these cells back to center stage, their enormous plasticity and heterogeneity, during both homeostasis and disease, are far from understood. At the same time, the ongoing revolution in single-cell genomics, with single-cell RNA sequencing (scRNA-seq) leading the way, promises to change this. Prevailing models of hematopoiesis with distinct intermediates are challenged by scRNA-seq data suggesting more continuous developmental trajectories in the myeloid cell compartment. Cell subset structures previously defined by protein marker expression need to be revised based on unbiased analyses of scRNA-seq data. Particularly in inflammatory conditions, myeloid cells exhibit substantially vaster heterogeneity than previously anticipated, and work performed within large international projects, such as the Human Cell Atlas, has already revealed novel tissue macrophage subsets. Based on these exciting developments, we propose the next steps to a full understanding of the myeloid cell compartment in health and diseases.
Topics: Animals; Biomarkers; Cell Differentiation; Cell Plasticity; Cellular Microenvironment; Homeostasis; Humans; Inflammation; Myeloid Cells; Sequence Analysis, RNA
PubMed: 30649988
DOI: 10.1146/annurev-immunol-042718-041728 -
Signal Transduction and Targeted Therapy Oct 2021Varying differentiation of myeloid cells is common in tumors, inflammation, autoimmune diseases, and metabolic diseases. The release of cytokines from myeloid cells is... (Review)
Review
Varying differentiation of myeloid cells is common in tumors, inflammation, autoimmune diseases, and metabolic diseases. The release of cytokines from myeloid cells is an important driving factor that leads to severe COVID-19 cases and subsequent death. This review briefly summarizes the results of single-cell sequencing of peripheral blood, lung tissue, and cerebrospinal fluid of COVID-19 patients and describes the differentiation trajectory of myeloid cells in patients. Moreover, we describe the function and mechanism of abnormal differentiation of myeloid cells to promote disease progression. Targeting myeloid cell-derived cytokines or checkpoints is essential in developing a combined therapeutic strategy for patients with severe COVID-19.
Topics: Animals; COVID-19; Cell Differentiation; Cellular Microenvironment; Humans; Myeloid Cells; SARS-CoV-2; Single-Cell Analysis
PubMed: 34707085
DOI: 10.1038/s41392-021-00792-0 -
Annals of the New York Academy of... Sep 2021On May 2017, the World Health Organization recognized sepsis as a global health priority. Sepsis profoundly perturbs immune homeostasis by initiating a complex response... (Review)
Review
On May 2017, the World Health Organization recognized sepsis as a global health priority. Sepsis profoundly perturbs immune homeostasis by initiating a complex response that varies over time, with the concomitant occurrence of pro- and anti-inflammatory mechanisms. Sepsis deeply impacts myeloid cell response. Different mechanisms are at play, such as apoptosis, endotoxin tolerance, metabolic failure, epigenetic reprogramming, and central regulation. This induces systemic effects on circulating immune cells and impacts progenitors locally in lymphoid organs. In the bone marrow, a progressive shift toward the release of immature myeloid cells (including myeloid-derived suppressor cells), at the expense of mature neutrophils, takes place. Circulating dendritic cell number remains dramatically low and monocytes/macrophages display an anti-inflammatory phenotype and reduced antigen presentation capacity. Intensity and persistence of these alterations are associated with increased risk of deleterious outcomes in patients. Thus, myeloid cells dysfunctions play a prominent role in the occurrence of sepsis-acquired immunodeficiency. For the most immunosuppressed patients, this paves the way for clinical trials evaluating immunoadjuvant molecules (granulocyte-macrophage colony-stimulating factor and interferon gamma) aimed at restoring homeostatic myeloid cell response. Our review offers a summary of sepsis-induced myeloid cell dysfunctions and current therapeutic strategies proposed to target these defects in patients.
Topics: Animals; Biomarkers; Disease Susceptibility; Humans; Immunocompromised Host; Immunologic Deficiency Syndromes; Myeloid Cells; Myeloid-Derived Suppressor Cells; Organ Specificity; Sepsis
PubMed: 32202669
DOI: 10.1111/nyas.14333 -
Microbiology Spectrum Nov 2016Given the dual and intrinsically contradictory roles of myeloid cells in both protective and yet also damaging effects of inflammatory and immunological processes, we... (Review)
Review
Given the dual and intrinsically contradictory roles of myeloid cells in both protective and yet also damaging effects of inflammatory and immunological processes, we suggest that it is important to consider the mechanisms and circumstances by which these cells are removed, either in the normal unchallenged state or during inflammation or disease. In this essay we address these subjects from a conceptual perspective, focusing as examples on four main myeloid cell types (neutrophils, monocytes, macrophages, and myeloid dendritic cells) and their clearance from the circulation or from naive and inflamed tissues. While the primary clearance process appears to involve endocytic uptake into macrophages, various tissue cell types can also recognize and remove dying cells, though their overall quantitative contribution is unclear. In fact, surprisingly, given the wealth of study in this area over the last 30 years, our conclusion is that we are still challenged with a substantial lack of mechanistic and regulatory understanding of when, how, and by what mechanisms migratory myeloid cells come to die and are recognized as needing to be removed, and indeed the precise processes of uptake of either the intact or fragmented cells. This reflects the extreme complexity and inherent redundancy of the clearance processes and argues for substantial investigative effort in this arena. In addition, it leads us to a sense that approaches to significant therapeutic modulation of selective myeloid clearance are still a long way off.
Topics: Animals; Autoimmune Diseases; Cell Movement; Granulomatous Disease, Chronic; Humans; Inflammation; Lupus Erythematosus, Systemic; Lymph Nodes; Lymphohistiocytosis, Hemophagocytic; Myeloid Cells
PubMed: 27837740
DOI: 10.1128/microbiolspec.MCHD-0005-2015 -
Current Opinion in Hematology Jul 2022Myeloid cells - granulocytes, monocytes, macrophages and dendritic cells (DCs) - are innate immune cells that play key roles in pathogen defense and inflammation, as... (Review)
Review
PURPOSE OF REVIEW
Myeloid cells - granulocytes, monocytes, macrophages and dendritic cells (DCs) - are innate immune cells that play key roles in pathogen defense and inflammation, as well as in tissue homeostasis and repair. Over the past 5 years, in part due to more widespread use of single cell omics technologies, it has become evident that these cell types are significantly more heterogeneous than was previously appreciated. In this review, we consider recent studies that have demonstrated heterogeneity among neutrophils, monocytes, macrophages and DCs in mice and humans. We also discuss studies that have revealed the sources of their heterogeneity.
RECENT FINDINGS
Recent studies have confirmed that ontogeny is a key determinant of diversity, with specific subsets of myeloid cells arising from distinct progenitors. However, diverse microenvironmental cues also strongly influence myeloid fate and function. Accumulating evidence therefore suggests that a combination of these mechanisms underlies myeloid cell diversity.
SUMMARY
Consideration of the heterogeneity of myeloid cells is critical for understanding their diverse activities, such as the role of macrophages in tissue damage versus repair, or tumor growth versus elimination. Insights into these mechanisms are informing the design of novel therapeutic approaches.
Topics: Animals; Dendritic Cells; Granulocytes; Humans; Inflammation; Macrophages; Mice; Monocytes; Myeloid Cells
PubMed: 35285448
DOI: 10.1097/MOH.0000000000000716 -
Current Opinion in Cell Biology Feb 2024Tissue-resident myeloid cells sense and transduce mechanical signals such as stiffness, stretch and compression. In the past two years, our understanding of the... (Review)
Review
Tissue-resident myeloid cells sense and transduce mechanical signals such as stiffness, stretch and compression. In the past two years, our understanding of the mechanosensitive signalling pathways in myeloid cells has significantly expanded. Moreover, it is increasingly clear which mechanical signals induce myeloid cells towards a pro- or anti-inflammatory phenotype. This is especially relevant in the context of altered matrix mechanics in immune-related pathologies or in the response to implanted biomaterials. A detailed understanding of myeloid cell mechanosensing may eventually lead to more effective cell-based immunotherapies for cancer, the development of mechanically inspired therapies to target fibrosis, and the engineering of safer implants. This review covers these recent advances in the emerging field of mechanoimmunology of myeloid cells.
Topics: Humans; Signal Transduction; Neoplasms; Biophysics; Myeloid Cells; Mechanotransduction, Cellular
PubMed: 38176349
DOI: 10.1016/j.ceb.2023.102311 -
Microbiology Spectrum Jan 2017Asthma is a heterogeneous chronic inflammatory disorder of the airways, and not surprisingly, many myeloid cells play a crucial role in pathogenesis. Antigen-presenting... (Review)
Review
Asthma is a heterogeneous chronic inflammatory disorder of the airways, and not surprisingly, many myeloid cells play a crucial role in pathogenesis. Antigen-presenting dendritic cells are the first to recognize the allergens, pollutants, and viruses that are implicated in asthma pathogenesis, and subsequently initiate the adaptive immune response by migrating to lymph nodes. Eosinophils are the hallmark of type 2 inflammation, releasing toxic compounds in the airways and contributing to airway remodeling. Mast cells and basophils control both the early- and late-phase allergic response and contribute to alterations in smooth muscle reactivity. Finally, relatively little is known about neutrophils and macrophages in this disease. Although many of these myeloid cells respond well to treatment with inhaled steroids, there is now an increasing armamentarium of targeted biologicals that can specifically eliminate only one myeloid cell population, like eosinophils. It is only with those new tools that we will be able to fully understand the role of myeloid cells in chronic asthma in humans.
Topics: Animals; Asthma; Chronic Disease; Humans; Myeloid Cells
PubMed: 28102118
DOI: 10.1128/microbiolspec.MCHD-0053-2016 -
Advances in Immunology 2020Immune responses are often accompanied by radical changes of cellular metabolism of immune cells. On the other hand, an ever increasing number of metabolic pathways and... (Review)
Review
Immune responses are often accompanied by radical changes of cellular metabolism of immune cells. On the other hand, an ever increasing number of metabolic pathways and products have been found to possess immune regulatory functions. The field of immunometabolism that investigates the interplay between metabolism and immunity has developed rapidly during the past decade. In this chapter, we attempt to summarize the recent progresses by scientists in China on metabolic regulation of innate immunity from the following three perspectives: metabolic regulation of myeloid cell functions, metabolic adaptations of tissue resident myeloid cells, and metabolism and immunity at the mucosal surfaces.
Topics: Adipose Tissue; Animals; Energy Metabolism; Fatty Liver; Humans; Immunity, Innate; Intestinal Mucosa; Kupffer Cells; Macrophages; Metabolic Networks and Pathways; Myeloid Cells; Tumor Microenvironment
PubMed: 32081196
DOI: 10.1016/bs.ai.2019.11.005 -
Frontiers in Immunology 2023Adipose tissue inflammation has been implicated in various chronic inflammatory diseases and cancer. Perivascular adipose tissue (PVAT) surrounds the aorta as an extra... (Review)
Review
Adipose tissue inflammation has been implicated in various chronic inflammatory diseases and cancer. Perivascular adipose tissue (PVAT) surrounds the aorta as an extra layer and was suggested to contribute to atherosclerosis development. PVAT regulates the function of endothelial and vascular smooth muscle cells in the aorta and represent a reservoir for various immune cells which may participate in aortic inflammation. Recent studies demonstrate that adipocytes also express various cytokine receptors and, therefore, may directly respond to inflammatory stimuli. Here we will summarize current knowledge on immune mechanisms regulating adipocyte activation and the crosstalk between myeloid cells and adipocytes in pathogenesis of atherosclerosis.
Topics: Humans; Adipose Tissue; Adipocytes; Atherosclerosis; Inflammation; Myeloid Cells
PubMed: 37781401
DOI: 10.3389/fimmu.2023.1238664