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Frontiers in Immunology 2019The tumor microenvironment (TME) of diverse cancer types is often characterized by high levels of infiltrating myeloid cells including monocytes, macrophages, dendritic... (Review)
Review
The tumor microenvironment (TME) of diverse cancer types is often characterized by high levels of infiltrating myeloid cells including monocytes, macrophages, dendritic cells, and granulocytes. These cells perform a variety of functions in the TME, varying from immune suppressive to immune stimulatory roles. In this review, we summarize the different myeloid cell populations in the TME and the intratumoral myeloid targeting approaches that are being clinically investigated, and discuss strategies that identify new myeloid subpopulations within the TME. The TME therapies include agents that modulate the functional activities of myeloid populations, that impact recruitment and survival of myeloid subpopulations, and that functionally reprogram or activate myeloid populations. We discuss the benefits, limitations and potential side effects of these therapeutic approaches.
Topics: Animals; Biomarkers; Cell Differentiation; Cell Proliferation; Cell Survival; Dendritic Cells; Humans; Immunomodulation; Macrophages; Monocytes; Myeloid Cells; Neoplasms; Neutrophils; Tumor Microenvironment
PubMed: 31402908
DOI: 10.3389/fimmu.2019.01611 -
Frontiers in Immunology 2022Alcoholic liver disease (ALD) is a leading chronic liver disease in which immune cells play a vital role. Myeloid cells have been extensively studied in ALD, including... (Review)
Review
Alcoholic liver disease (ALD) is a leading chronic liver disease in which immune cells play a vital role. Myeloid cells have been extensively studied in ALD, including granulocytes, macrophages, monocytes, and dendritic cells, which are involved in the occurrence and progression of steatosis, inflammation, fibrosis, and eventual cirrhosis. These cells can be popularly targeted and regulated by factors from different sources, including cytokines secreted by other cells, extracellular vesicles, and substances in serum-for example, infiltration of monocytes or neutrophils, activation of Kupffer cells, and polarization of macrophages. These processes can affect and change the function and phenotype of myeloid cells. Here we mainly review the key mediators that affect the infiltration and function of mainly myeloid cells in ALD as well as their regulatory mechanisms on target cells, which may provide novel immunotherapeutic approaches. The single-cell multimodal omics of myeloid cells is also discussed to help transform them into basic research or therapeutic strategy of ALD clinically.
Topics: Cytokines; Fatty Liver; Humans; Kupffer Cells; Liver Diseases, Alcoholic; Myeloid Cells
PubMed: 36032154
DOI: 10.3389/fimmu.2022.971346 -
Current Opinion in Hematology Jan 2021Understanding the fast-moving field of single-cell technologies, as applied to myeloid biology, requires an appreciation of basic molecular, informatics, and biological... (Review)
Review
PURPOSE OF REVIEW
Understanding the fast-moving field of single-cell technologies, as applied to myeloid biology, requires an appreciation of basic molecular, informatics, and biological concepts. Here, we highlight both key and recent articles to illustrate basic concepts for those new to molecular single-cell analyses in myeloid hematology.
RECENT FINDINGS
Recent studies apply single-cell omics to discover novel cell populations, construct relationships between cell populations, reconfigure the organization of hematopoiesis, and study hematopoietic lineage tree and fate choices. Accompanying development of technologies, new informatic tools have emerged, providing exciting new insights.
SUMMARY
Hematopoietic stem and progenitor cells are regulated by complex intrinsic and extrinsic factors to produce blood cell types. In this review, we discuss recent advances in single-cell omics to profile these cells, methods to infer cell type identify, and trajectories from molecular omics data to ultimately derive new insights into hematopoietic stem and progenitor cell biology. We further discuss future applications of these technologies to understand hematopoietic cell interactions, function, and development. The goal is to offer a comprehensive overview of current single-cell technologies and their impact on our understanding of myeloid cell development for those new to single-cell analyses.
Topics: Animals; Cell Communication; Genomics; Hematopoiesis; Hematopoietic Stem Cells; Humans; Myeloid Cells; Single-Cell Analysis
PubMed: 33186153
DOI: 10.1097/MOH.0000000000000623 -
Advanced Biology Mar 2021Cancer is the outcome of the conflict between the host immune system and cancer cells. The crosstalk between immune cells and tumor cells within the tumor... (Review)
Review
Cancer is the outcome of the conflict between the host immune system and cancer cells. The crosstalk between immune cells and tumor cells within the tumor microenvironment (TME) influences tumor progression and metastasis. Many studies have clarified the cellular and molecular events that can induce cancer cells to escape immune surveillance, including those involving tumor-induced myeloid cell-mediated immunosuppression. Emerging evidence indicates that tumor-infiltrating myeloid cells (TIMs) accelerate tumor growth and induce angiogenesis, metastasis, and therapy resistance once converted into potent immunosuppressive cells. Here, how tumor infiltrating myeloid cells participate in tumor immune evasion and the prospects of these cells in cancer immunotherapy are discussed.
Topics: Humans; Immunotherapy; Myeloid Cells; Neoplasms; Tumor Escape; Tumor Microenvironment
PubMed: 33729699
DOI: 10.1002/adbi.201900311 -
Immunological Reviews Mar 2021Most, if not all, aspects of carcinogenesis are influenced by the tumor microenvironment (TME), a complex architecture of cells, matrix components, soluble signals, and... (Review)
Review
Most, if not all, aspects of carcinogenesis are influenced by the tumor microenvironment (TME), a complex architecture of cells, matrix components, soluble signals, and their dynamic interactions in the context of physical traits of the tissue. Expanding application of technologies for high-dimensional analyses with single-cell resolution has begun to decipher the contributions of the immune system to cancer progression and its implications for therapy. In this review, we will discuss the multifaceted roles of tumor-associated macrophages and neutrophils, focusing on factors that subvert tissue immune homeostasis and offer therapeutic opportunities for TME reprogramming. By performing a critical analysis of available datasets, we elaborate on diversification mechanisms and unifying principles of myeloid cell heterogeneity in human tumors.
Topics: Carcinogenesis; Humans; Myeloid Cells; Neoplasms; Neutrophils; Tumor Microenvironment
PubMed: 33565148
DOI: 10.1111/imr.12944 -
Frontiers in Immunology 2019Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells with major regulatory functions and rise during pathological... (Review)
Review
Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells with major regulatory functions and rise during pathological conditions, including cancer, infections and autoimmune conditions. MDSC expansion is generally linked to inflammatory processes that emerge in response to stable immunological stress, which alter both magnitude and quality of the myelopoietic output. Inability to reinstate physiological myelopoiesis would fall in an "emergency state" that perpetually reprograms myeloid cells toward suppressive functions. While differentiation and reprogramming of myeloid cells toward an immunosuppressive phenotype can be considered the result of a multistep process that originates in the bone marrow and culminates in the tumor microenvironment, the identification of its driving events may offer potential therapeutic approaches in different pathologies. Indeed, whereas expansion of MDSCs, in both murine and human tumor bearers, results in reduced immune surveillance and antitumor cytotoxicity, placing an obstacle to the effectiveness of anticancer therapies, adoptive transfer of MDSCs has shown therapeutic benefits in autoimmune disorders. Here, we describe relevant mechanisms of myeloid cell reprogramming leading to generation of suppressive MDSCs and discuss their therapeutic ductility in disease.
Topics: Animals; Autoimmunity; Humans; Immune Tolerance; Myeloid-Derived Suppressor Cells; Neoplasms
PubMed: 31130949
DOI: 10.3389/fimmu.2019.00949 -
Journal of Neuroimmunology Aug 2018The past decade has revealed much about the complexity of the local inflammatory response after spinal cord injury (SCI). A major challenge is to distinguish between... (Review)
Review
The past decade has revealed much about the complexity of the local inflammatory response after spinal cord injury (SCI). A major challenge is to distinguish between microglia and monocyte-derived macrophages (MDMs) to determine their phenotype and function. Transcriptome studies have revealed microglia-selective genes but are still limited in scope because many markers are downregulated after injury. Additionally, new genetic reporter mice are available to study microglia and MDMs. There is more evidence now for the plasticity and heterogeneity of microglia and MDMs. We also discuss the role of neutrophils that are the first peripheral cells to enter the injured CNS.
Topics: Animals; Humans; Immunity, Cellular; Macrophages; Microglia; Monocytes; Myeloid Cells; Neutrophils; Spinal Cord Injuries
PubMed: 29957394
DOI: 10.1016/j.jneuroim.2018.06.003 -
Microbiology Spectrum Apr 2016Myeloid cells have diverse roles in regulating immunity, inflammation, and extracellular matrix turnover. To accomplish these tasks, myeloid cells carry an arsenal of... (Review)
Review
Myeloid cells have diverse roles in regulating immunity, inflammation, and extracellular matrix turnover. To accomplish these tasks, myeloid cells carry an arsenal of metalloproteinases, which include the matrix metalloproteinases and the adamalysins. These enzymes have diverse substrate repertoires, and are thus involved in mediating proteolytic cascades, cell migration, and cell signaling. Dysregulation of metalloproteinases contributes to pathogenic processes, including inflammation, fibrosis, and cancer. Metalloproteinases also have important nonproteolytic functions in controlling cytoskeletal dynamics during macrophage fusion and enhancing transcription to promote antiviral immunity. This review highlights the diverse contributions of metalloproteinases to myeloid cell functions.
Topics: Animals; Humans; Metalloproteases; Myeloid Cells
PubMed: 27227311
DOI: 10.1128/microbiolspec.MCHD-0002-2015 -
Microbiology Spectrum Oct 2016Lectins recognize a diverse array of carbohydrate structures and perform numerous essential biological functions. Here we focus on only two families of lectins, the... (Review)
Review
Lectins recognize a diverse array of carbohydrate structures and perform numerous essential biological functions. Here we focus on only two families of lectins, the Siglecs and C-type lectins. Triggering of intracellular signaling cascades following ligand recognition by these receptors can have profound effects on the induction and modulation of immunity. In this chapter, we provide a brief overview of each family and then focus on selected examples that highlight how these lectins can influence myeloid cell functioning in health and disease. Receptors that are discussed include Sn (Siglec-1), CD33 (Siglec-3), and Siglec-5, -7, -8, -9, -10, -11, -14, -15, -E, -F, and -G as well as Dectin-1, MICL, Dectin-2, Mincle/MCL, and the macrophage mannose receptor.
Topics: Animals; Humans; Myeloid Cells; Receptors, Mitogen
PubMed: 27780012
DOI: 10.1128/microbiolspec.MCHD-0036-2016 -
International Journal of Molecular... Sep 2018AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine kinase consisting of the arrangement of various α β, and γisoforms that are expressed... (Review)
Review
AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine kinase consisting of the arrangement of various α β, and γisoforms that are expressed differently depending on the tissue or the cell lineage. AMPK is one of the major sensors of energy status in mammalian cells and as such plays essential roles in the regulation of cellular homeostasis, metabolism, cell growth, differentiation, apoptosis, and autophagy. AMPK is activated by two upstream kinases, the tumor suppressor liver kinase B1 (LKB1) and the calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) through phosphorylation of the kinase on Thr172, leading to its activation. In addition, AMPK inhibits the mTOR pathway through phosphorylation and activation of tuberous sclerosis protein 2 (TSC2) and causes direct activation of unc-51-like autophagy activating kinase 1 (ULK1) via phosphorylation of Ser555, thus promoting initiation of autophagy. Although it is well established that AMPK can control the differentiation of different cell lineages, including hematopoietic stem cells (HSCs), progenitors, and mature hematopoietic cells, the role of AMPK regarding myeloid cell differentiation is less documented. The differentiation of monocytes into macrophages triggered by colony stimulating factor 1 (CSF-1), a process during which both caspase activation (independently of apoptosis induction) and AMPK-dependent stimulation of autophagy are necessary, is one noticeable example of the involvement of AMPK in the physiological differentiation of myeloid cells. The present review focuses on the role of AMPK in the regulation of the physiological and pathological differentiation of myeloid cells. The mechanisms of autophagy induction by AMPK will also be addressed, as autophagy has been shown to be important for differentiation of hematopoietic cells. In addition, myeloid malignancies (myeloid leukemia or dysplasia) are characterized by profound defects in the establishment of proper differentiation programs. Reinduction of a normal differentiation process in myeloid malignancies has thus emerged as a valuable and promising therapeutic strategy. As AMPK seems to exert a key role in the differentiation of myeloid cells, notably through induction of autophagy, we will also discuss the potential to target this pathway as a pro-differentiating and anti-leukemic strategy in myeloid malignancies.
Topics: AMP-Activated Protein Kinases; Animals; Cell Differentiation; Enzyme Activation; Hematologic Neoplasms; Hematopoietic Stem Cells; Humans; Myeloid Cells
PubMed: 30274374
DOI: 10.3390/ijms19102991