-
Nature Medicine Jun 2018Recent advances in cell tracing and sequencing technologies have expanded our knowledge on leukocyte behavior. As a consequence, inflammatory cells, such as... (Review)
Review
Recent advances in cell tracing and sequencing technologies have expanded our knowledge on leukocyte behavior. As a consequence, inflammatory cells, such as monocyte-derived macrophages, and their actions and products are increasingly being considered as potential drug targets for treatment of atherosclerosis, myocardial infarction and heart failure. Particularly promising developments are the identification of harmful arterial and cardiac macrophage subsets, the cells' altered, sometimes even clonal production in hematopoietic organs, and epigenetically entrained memories of myeloid progenitors and macrophages in the setting of cardiovascular disease. Given the roles of monocytes and macrophages in host defense, intricately understanding the involved cellular subsets, sources and functions is essential for the design of precision therapeutics that preserve protective innate immunity. Here I review how new clinical and preclinical data, often linking the cardiovascular, immune and other organ systems, propel conceptual advances to a point where cardiovascular immunotherapy appears within reach.
Topics: Animals; Cardiovascular Diseases; Humans; Immunity, Innate; Immunotherapy; Inflammation; Myeloid Cells; Risk Factors
PubMed: 29867229
DOI: 10.1038/s41591-018-0064-0 -
Cancer Research Jan 2022Immunosuppressive myeloid cells play a major role in cancer by negatively regulating immune responses, promoting tumor progression, and limiting the efficacy of cancer... (Review)
Review
Immunosuppressive myeloid cells play a major role in cancer by negatively regulating immune responses, promoting tumor progression, and limiting the efficacy of cancer immunotherapy. Immunosuppression is mediated by various mechanisms dependent upon the type of myeloid cell involved. In recent years, a more universal mechanism of immunosuppressive activity of myeloid cells has emerged: Generation of oxidized lipids. Oxidized lipids accumulate in all types of myeloid cells and are often transferred between cells. In this review, we discuss mechanisms involved in the generation and biological role of myeloid cell-derived oxidized lipids in cancer.
Topics: Animals; Humans; Immune Tolerance; Lipid Metabolism; Myeloid Cells; Neoplasms; Oxidation-Reduction; Tumor Microenvironment
PubMed: 34764204
DOI: 10.1158/0008-5472.CAN-21-3054 -
Advanced Drug Delivery Reviews Jun 2023In the presence of tissue inflammation, injury, or cancer, myeloid cells are recruited to disease regions through a multi-step process involving myelopoiesis,... (Review)
Review
In the presence of tissue inflammation, injury, or cancer, myeloid cells are recruited to disease regions through a multi-step process involving myelopoiesis, chemotaxis, cell migration, and diapedesis. As an emerging drug delivery approach, cell-mediated drug delivery takes advantage of the cell recruitment process to enhance the active transport of therapeutic cargo to disease regions. In the past few decades, a variety of nano-engineering methods have emerged to enhance interactions of nanoparticles with cells of interest, which can be adapted for cell-mediated drug delivery. Moreover, the drug delivery field can benefit from the recent clinical success of cell-based therapies, which created cell-engineering methods to engineer circulating leukocytes as 'living drug delivery vehicles' to target diseased tissues. In this review, we first provide an overview of myeloid cell recruitment and discuss how various factors within this process may affect cell-mediated delivery. In the second part of this review article, we summarize the status quo of nano-engineering and cell-engineering approaches and discuss how these engineering approaches can be adapted for cell-mediated delivery. Finally, we discuss future directions of this field, pointing out key challenges in the clinical translation of cell-mediated drug delivery.
Topics: Humans; Drug Carriers; Nanomedicine; Drug Delivery Systems; Nanoparticles; Myeloid Cells; Cell- and Tissue-Based Therapy
PubMed: 37068659
DOI: 10.1016/j.addr.2023.114827 -
Frontiers in Immunology 2024
Topics: Humans; Cellular Reprogramming; Myeloid Cells; Animals; Signal Transduction
PubMed: 38745655
DOI: 10.3389/fimmu.2024.1414482 -
European Journal of Immunology Oct 2023Experimental autoimmune encephalomyelitis (EAE) is an animal model of central nervous system (CNS) autoimmunity. It is most commonly used to mimic aspects of multiple... (Review)
Review
Experimental autoimmune encephalomyelitis (EAE) is an animal model of central nervous system (CNS) autoimmunity. It is most commonly used to mimic aspects of multiple sclerosis (MS), a demyelinating disorder of the human brain and spinal cord. The innate immune response displays one of the core pathophysiological features linked to both the acute and chronic stages of MS. Hence, understanding and targeting the innate immune response is essential. Microglia and other CNS resident MUs, as well as infiltrating myeloid cells, diverge substantially in terms of both their biology and their roles in EAE. Recent advances in the field show that antigen presentation, as well as disease-propagating and regulatory interactions with lymphocytes, can be attributed to specific myeloid cell types and cell states in EAE lesions, following a distinct temporal pattern during disease initiation, propagation and recovery. Furthermore, single-cell techniques enable the assessment of characteristic proinflammatory as well as beneficial cell states, and identification of potential treatment targets. Here, we discuss the principles of EAE induction and protocols for varying experimental paradigms, the composition of the myeloid compartment of the CNS during health and disease, and systematically review effects on myeloid cells for therapeutic approaches in EAE.
Topics: Animals; Humans; Mice; Encephalomyelitis, Autoimmune, Experimental; Central Nervous System; Multiple Sclerosis; Spinal Cord; Myeloid Cells; Mice, Inbred C57BL
PubMed: 37505465
DOI: 10.1002/eji.202250234 -
Histology and Histopathology Apr 2016Multiple sclerosis (MS) is a demyelinating disease in which an exacerbated immune response provokes oligodendrocyte loss and demyelination, the hallmarks of this... (Review)
Review
Multiple sclerosis (MS) is a demyelinating disease in which an exacerbated immune response provokes oligodendrocyte loss and demyelination, the hallmarks of this neurological disease. The destruction of myelin due to the uncontrolled activity of the invading immune cells leads to the formation of MS plaques. Among the different leukocytes that participate in the immune response associated with MS, the role of myeloid cells has been analyzed extensively (i.e. macrophages, dendritic cells -DCs- and neutrophils). Hence, in this review we will summarize what is known about the distribution, expression and markers available to study myeloid cells, and their histopathology, not only in a standard animal model of MS (autoimmune experimental encephalomyelitis -EAE) but also in MS tissue. In this review, we will not only refer to mature myeloid cells but also to the undifferentiated and almost unexplored myeloid-derived suppressor cells (MDSCs). The active role of MDSCs in the prompt resolution of an immune episode is gaining importance, yet is still the subject of some debate. Finally, the similarities and differences between MS and EAE are discussed, particularly in terms of myeloid cell phenotype, activity and the markers used.
Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; Humans; Multiple Sclerosis; Myeloid Cells
PubMed: 26592711
DOI: 10.14670/HH-11-699 -
Advances in Immunology 2023Myeloid cells, particularly macrophages, act as the frontline responders to infectious agents and initiate inflammation. While the molecular mechanisms driving... (Review)
Review
Myeloid cells, particularly macrophages, act as the frontline responders to infectious agents and initiate inflammation. While the molecular mechanisms driving inflammatory responses have primarily focused on pattern recognition by myeloid cells and subsequent transcriptional events, it is crucial to note that post-transcriptional regulation plays a pivotal role in this process. In addition to the transcriptional regulation of innate immune responses, additional layers of intricate network of post-transcriptional mechanisms critically determine the quantity and duration of key inflammatory products and thus the outcome of immune responses. A multitude of mechanisms governing post-transcriptional regulation in innate immunity have been uncovered, encompassing RNA alternative splicing, mRNA stability, and translational regulation. This review encapsulates the current insights into the post-transcriptional regulation of inflammatory genes within myeloid cells, with particular emphasis on translational regulation during inflammation. While acknowledging the advancements, we also shed light on the existing gaps in immunological research pertaining to post-transcriptional levels and propose perspectives that controlling post-transcriptional process may serve as potential targets for therapeutic interventions in inflammatory diseases.
Topics: Humans; Immunity, Innate; Inflammation; Myeloid Cells; Macrophages; Alternative Splicing
PubMed: 38042586
DOI: 10.1016/bs.ai.2023.09.001 -
Breast Cancer Research : BCR Jun 2023Breast cancer presents as one of the top health threats to women around the world. Myeloid cells are the most abundant cells and the major immune coordinator in breast...
BACKGROUND
Breast cancer presents as one of the top health threats to women around the world. Myeloid cells are the most abundant cells and the major immune coordinator in breast cancer tumor microenvironment (TME), target therapies that harness the anti-tumor potential of myeloid cells are currently being evaluated in clinical trials. However, the landscape and dynamic transition of myeloid cells in breast cancer TME are still largely unknown.
METHODS
Myeloid cells were characterized in the single-cell data and extracted with a deconvolution algorithm to be assessed in bulk-sequencing data. We used the Shannon index to describe the diversity of infiltrating myeloid cells. A 5-gene surrogate scoring system was then constructed and evaluated to infer the myeloid cell diversity in a clinically feasible manner.
RESULTS
We dissected the breast cancer infiltrating myeloid cells into 15 subgroups including macrophages, dendritic cells (DCs), and monocytes. Mac_CCL4 had the highest angiogenic activity, Mac_APOE and Mac_CXCL10 were highly active in cytokine secretion, and the DCs had upregulated antigen presentation pathways. The infiltrating myeloid diversity was calculated in the deconvoluted bulk-sequencing data, and we found that higher myeloid diversity was robustly associated with more favorable clinical outcomes, higher neoadjuvant therapy responses, and a higher rate of somatic mutations. We then used machine learning methods to perform feature selection and reduction, which generated a clinical-friendly scoring system consisting of 5 genes (C3, CD27, GFPT2, GMFG, and HLA-DPB1) that could be used to predict clinical outcomes in breast cancer patients.
CONCLUSIONS
Our study explored the heterogeneity and plasticity of breast cancer infiltrating myeloid cells. By using a novel combination of bioinformatic approaches, we proposed the myeloid diversity index as a new prognostic metric and constructed a clinically practical scoring system to guide future patient evaluation and risk stratification.
Topics: Humans; Female; Breast Neoplasms; Myeloid Cells; Macrophages; Monocytes; Prognosis; Tumor Microenvironment
PubMed: 37287069
DOI: 10.1186/s13058-023-01669-6 -
Frontiers in Immunology 2023
Topics: Multiomics; Myeloid Cells; Myeloid Progenitor Cells
PubMed: 37799726
DOI: 10.3389/fimmu.2023.1292400 -
Frontiers in Immunology 2020Amino acid metabolism is a critical regulator of the immune response, and its modulating becomes a promising approach in various forms of immunotherapy. Insufficient... (Review)
Review
Amino acid metabolism is a critical regulator of the immune response, and its modulating becomes a promising approach in various forms of immunotherapy. Insufficient concentrations of essential amino acids restrict T-cells activation and proliferation. However, only arginases, that degrade L-arginine, as well as enzymes that hydrolyze L-tryptophan are substantially increased in cancer. Two arginase isoforms, ARG1 and ARG2, have been found to be present in tumors and their increased activity usually correlates with more advanced disease and worse clinical prognosis. Nearly all types of myeloid cells were reported to produce arginases and the increased numbers of various populations of myeloid-derived suppressor cells and macrophages correlate with inferior clinical outcomes of cancer patients. Here, we describe the role of arginases produced by myeloid cells in regulating various populations of immune cells, discuss molecular mechanisms of immunoregulatory processes involving L-arginine metabolism and outline therapeutic approaches to mitigate the negative effects of arginases on antitumor immune response. Development of potent arginase inhibitors, with improved pharmacokinetic properties, may lead to the elaboration of novel therapeutic strategies based on targeting immunoregulatory pathways controlled by L-arginine degradation.
Topics: Animals; Antineoplastic Agents; Arginase; Arginine; Clinical Trials as Topic; Humans; Macrophages; Mice; Myeloid Cells; Myeloid Progenitor Cells; Neoplasms
PubMed: 32499785
DOI: 10.3389/fimmu.2020.00938