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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 -
Frontiers in Immunology 2021
Topics: Animals; Biomarkers; Blood Platelets; Cell Communication; Disease Management; Disease Susceptibility; Humans; Immunotherapy; Killer Cells, Natural; Myeloid Cells; Myeloid-Derived Suppressor Cells; Neoplasms; Tumor Microenvironment
PubMed: 34276709
DOI: 10.3389/fimmu.2021.718844 -
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 -
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 -
Frontiers in Immunology 2023Colorectal cancer (CRC) is the third most predominant malignancy in the world. Although the importance of immune system in cancer development has been well established,...
Colorectal cancer (CRC) is the third most predominant malignancy in the world. Although the importance of immune system in cancer development has been well established, the underlying mechanisms remain to be investigated further. Here we studied a novel protein prokineticin 2 (Prok2, also known as Bv8) as a key pro-tumoral factor in CRC progression in and settings. Human colorectal tumor tissues, myeloid cell lines (U937 cells and HL60 cells) and colorectal cancer cell line (Caco-2 cells) were used for various studies. Myeloid cell infiltration (especially neutrophils) and Bv8 accumulation were detected in human colorectal tumor tissue with immunostaining. The chemotactic effects of Bv8 on myeloid cells were presented in the transwell assay and chemotaxis assy. Cultured CRC cells treated with myeloid cells or Bv8 produced reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF). Furthermore, ROS and VEGF acted as pro-angiogenesis buffer in myeloid cell-infiltrated CRC microenvironment. Moreover, myeloid cells or Bv8 enhanced energy consumption of glycolysis ATP and mitochondria ATP of CRC cells. Interestingly, myeloid cells increased CRC cell viability, but CRC cells decreased the viability of myeloid cells. ERK signalling pathway in CRC cells was activated in the presence of Bv8 or co-cultured myeloid cells. In conclusion, our data indicated the vital roles of Bv8 in myeloid cell infiltration and CRC development, suggesting that Bv8 may be a potential therapeutic target for colorectal cancer-related immunotherapy.
Topics: Humans; Vascular Endothelial Growth Factor A; Caco-2 Cells; Reactive Oxygen Species; Neuropeptides; Myeloid Cells; Cell Movement; Colorectal Neoplasms; Vascular Endothelial Growth Factors; Adenosine Triphosphate; Tumor Microenvironment
PubMed: 37090721
DOI: 10.3389/fimmu.2023.1158045 -
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 -
Physiological Reviews Apr 2018The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and... (Review)
Review
The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and PKR2. This signaling system has been linked to several important biological functions, including gastrointestinal tract motility, regulation of circadian rhythms, neurogenesis, angiogenesis and cancer progression, hematopoiesis, and nociception. Mutations in PKR2 or Bv8/PROK2 have been associated with Kallmann syndrome, a developmental disorder characterized by defective olfactory bulb neurogenesis, impaired development of gonadotropin-releasing hormone neurons, and infertility. Also, Bv8/PROK2 is strongly upregulated in neutrophils and other inflammatory cells in response to granulocyte-colony stimulating factor or other myeloid growth factors and functions as a pronociceptive mediator in inflamed tissues as well as a regulator of myeloid cell-dependent tumor angiogenesis. Bv8/PROK2 has been also implicated in neuropathic pain. Anti-Bv8/PROK2 antibodies or small molecule PKR inhibitors ameliorate pain arising from tissue injury and inhibit angiogenesis and inflammation associated with tumors or some autoimmune disorders.
Topics: Animals; Cell Movement; Humans; Inflammation; Inflammation Mediators; Myeloid Cells; Neurotransmitter Agents; Receptors, G-Protein-Coupled
PubMed: 29537336
DOI: 10.1152/physrev.00012.2017 -
Journal of Internal Medicine May 2019Myeloid cells assume a wide range of phenotypes, some of which are protective against injury and infection whilst others promote cardiovascular disease. This... (Review)
Review
Myeloid cells assume a wide range of phenotypes, some of which are protective against injury and infection whilst others promote cardiovascular disease. This heterogeneity is partially caused by switching of cell sources from local tissue-resident macrophage proliferation to recruitment of circulating cells, and partially due to macrophages' phenotypic plasticity. While long-lived tissue-resident macrophages support development, tissue homoeostasis and cardiac conduction, monocyte-derived cells may promote destruction of the arterial wall and the myocardium, leading to organ ischaemia and heart failure. Influencing myeloid cell flux and phenotype shifts emerges as a therapeutic opportunity in many disease areas, including atherosclerosis, acute myocardial infarction, heart failure and stroke. However, it is currently unclear which cell subsets and drug targets are the most efficient and safest options. Here I review the neutrophil and macrophage supply chain and the cells' emerging heterogeneity in the setting of atherosclerosis and ischaemic heart disease.
Topics: Atherosclerosis; Cardiovascular Diseases; Humans; Myeloid Cells; Myocardial Ischemia
PubMed: 30585362
DOI: 10.1111/joim.12844 -
Journal of Thrombosis and Haemostasis :... Feb 2024Myeloid cell metabolic reprogramming is a hallmark of inflammatory disease; however, its role in inflammation-induced hypercoagulability is poorly understood.
BACKGROUND
Myeloid cell metabolic reprogramming is a hallmark of inflammatory disease; however, its role in inflammation-induced hypercoagulability is poorly understood.
OBJECTIVES
We aimed to evaluate the role of inflammation-associated metabolic reprogramming in regulating blood coagulation.
METHODS
We used novel myeloid cell-based global hemostasis assays and murine models of immunometabolic disease.
RESULTS
Glycolysis was essential for enhanced activated myeloid cell tissue factor expression and decryption, driving increased cell-dependent thrombin generation in response to inflammatory challenge. Similarly, inhibition of glycolysis enhanced activated macrophage fibrinolytic activity through reduced plasminogen activator inhibitor 1 activity. Macrophage polarization or activation markedly increased endothelial protein C receptor (EPCR) expression on monocytes and macrophages, leading to increased myeloid cell-dependent protein C activation. Importantly, inflammation-dependent EPCR expression on tissue-resident macrophages was also observed in vivo. Adipose tissue macrophages from obese mice fed a high-fat diet exhibited significantly enhanced EPCR expression and activated protein C generation compared with macrophages isolated from the adipose tissue of healthy mice. Similarly, the induction of colitis in mice prompted infiltration of EPCR innate myeloid cells within inflamed colonic tissue that were absent from the intestinal tissue of healthy mice.
CONCLUSION
Collectively, this study identifies immunometabolic regulation of myeloid cell hypercoagulability, opening new therapeutic possibilities for targeted mitigation of thromboinflammatory disease.
Topics: Animals; Mice; Protein C; Endothelial Protein C Receptor; Myeloid Cells; Inflammation; Thrombophilia; Glycolysis; Mice, Inbred C57BL
PubMed: 37865288
DOI: 10.1016/j.jtha.2023.10.006 -
Seminars in Immunology Jun 2021The dysregulation of myeloid cell responses is increasingly demonstrated to be a major mechanism of pathogenesis for COVID-19. The pathological cellular and cytokine... (Review)
Review
The dysregulation of myeloid cell responses is increasingly demonstrated to be a major mechanism of pathogenesis for COVID-19. The pathological cellular and cytokine signatures associated with this disease point to a critical role of a hyperactivated innate immune response in driving pathology. Unique immunopathological features of COVID-19 include myeloid-cell dominant inflammation and cytokine release syndrome (CRS) alongside lymphopenia and acute respiratory distress syndrome (ARDS), all of which correlate with severe disease. Studies suggest a range of causes mediating myeloid hyperactivation, such as aberrant innate sensing, asynchronized immune cellular responses, as well as direct viral protein/host interactions. These include the recent identification of new myeloid cell receptors that bind SARS-CoV-2, which drive myeloid cell hyperinflammatory responses independently of lung epithelial cell infection via the canonical receptor, angiotensin-converting enzyme 2 (ACE2). The spectrum and nature of myeloid cell dysregulation in COVID-19 also differs from, at least to some extent, what is observed in other infectious diseases involving myeloid cell activation. While much of the therapeutic effort has focused on preventative measures with vaccines or neutralizing antibodies that block viral infection, recent clinical trials have also targeted myeloid cells and the associated cytokines as a means to resolve CRS and severe disease, with promising but thus far modest effects. In this review, we critically examine potential mechanisms driving myeloid cell dysregulation, leading to immunopathology and severe disease, and discuss potential therapeutic strategies targeting myeloid cells as a new paradigm for COVID-19 treatment.
Topics: Humans; Immunity, Innate; Myeloid Cells; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34823995
DOI: 10.1016/j.smim.2021.101524