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Frontiers in Immunology 2020Natural killer (NK) cells are endowed with germline-encoded receptors that enable them to detect and kill malignant cells without prior priming. Over the years,... (Review)
Review
Natural killer (NK) cells are endowed with germline-encoded receptors that enable them to detect and kill malignant cells without prior priming. Over the years, overwhelming evidence has identified an essential role for NK cells in tumor immune surveillance. More recently, clinical trials have also highlighted their potential in therapeutic settings. Yet, data show that NK cells can be dysregulated within the tumor microenvironment (TME), rendering them ineffective in eradicating the cancer cells. This has been attributed to immune suppressive factors, including the tumor cells , stromal cells, regulatory T cells, and soluble factors such as reactive oxygen species and cytokines. However, the TME also hosts myeloid cells such as dendritic cells, macrophages, neutrophils, and myeloid-derived suppressor cells that influence NK cell function. Although the NK-myeloid cell crosstalk can promote anti-tumor responses, myeloid cells in the TME often dysregulate NK cells direct cell-to-cell interactions down-regulating key NK cell receptors, depletion of nutrients and growth factors required for NK cell growth, and secretion of metabolites, chemokines and cytokines that ultimately alter NK cell trafficking, survival, and cytotoxicity. Here, we review the complex functions of myeloid-derived cytokines in both supporting and suppressing NK cells in the TME and how NK cell-derived cytokines can influence myeloid subsets. We discuss challenges related to these interactions in unleashing the full potential of endogenous and adoptively infused NK cells. Finally, we present strategies aiming at improving NK cell-based cancer immunotherapies pathways that are involved in the NK-myeloid cell crosstalk in the TME.
Topics: Animals; Cell Communication; Cytokines; Humans; Immunotherapy; Killer Cells, Natural; Myeloid Cells; Neoplasms; Tumor Microenvironment
PubMed: 33584718
DOI: 10.3389/fimmu.2020.621225 -
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 -
Cellular and Molecular Life Sciences :... Sep 2021Different types of multinucleated giant cells (MGCs) of myeloid origin have been described; osteoclasts are the most extensively studied because of their importance in... (Review)
Review
Different types of multinucleated giant cells (MGCs) of myeloid origin have been described; osteoclasts are the most extensively studied because of their importance in bone homeostasis. MGCs are formed by cell-to-cell fusion, and most types have been observed in pathological conditions, especially in infectious and non-infectious chronic inflammatory contexts. The precise role of the different MGCs and the mechanisms that govern their formation remain poorly understood, likely due to their heterogeneity. First, we will introduce the main populations of MGCs derived from the monocyte/macrophage lineage. We will then discuss the known molecular actors mediating the early stages of fusion, focusing on cell-surface receptors involved in the cell-to-cell adhesion steps that ultimately lead to multinucleation. Given that cell-to-cell fusion is a complex and well-coordinated process, we will also describe what is currently known about the evolution of F-actin-based structures involved in macrophage fusion, i.e., podosomes, zipper-like structures, and tunneling nanotubes (TNT). Finally, the localization and potential role of the key fusion mediators related to the formation of these F-actin structures will be discussed. This review intends to present the current status of knowledge of the molecular and cellular mechanisms supporting multinucleation of myeloid cells, highlighting the gaps still existing, and contributing to the proposition of potential disease-specific MGC markers and/or therapeutic targets.
Topics: Cell Adhesion; Giant Cells; Humans; Integrins; Macrophages; Myeloid Cells; Osteoclasts; Osteogenesis; Podosomes; Receptors, Immunologic
PubMed: 34296319
DOI: 10.1007/s00018-021-03875-x -
Neurotherapeutics : the Journal of the... Apr 2011Traumatic spinal cord injury (SCI) affects the activation, migration, and function of microglia, neutrophils and monocyte/macrophages. Because these myeloid cells can... (Review)
Review
Traumatic spinal cord injury (SCI) affects the activation, migration, and function of microglia, neutrophils and monocyte/macrophages. Because these myeloid cells can positively and negatively affect survival of neurons and glia, they are among the most commonly studied immune cells. However, the mechanisms that regulate myeloid cell activation and recruitment after SCI have not been adequately defined. In general, the dynamics and composition of myeloid cell recruitment to the injured spinal cord are consistent between mammalian species; only the onset, duration, and magnitude of the response vary. Emerging data, mostly from rat and mouse SCI models, indicate that resident and recruited myeloid cells are derived from multiple sources, including the yolk sac during development and the bone marrow and spleen in adulthood. After SCI, a complex array of chemokines and cytokines regulate myelopoiesis and intraspinal trafficking of myeloid cells. As these cells accumulate in the injured spinal cord, the collective actions of diverse cues in the lesion environment help to create an inflammatory response marked by tremendous phenotypic and functional heterogeneity. Indeed, it is difficult to attribute specific reparative or injurious functions to one or more myeloid cells because of convergence of cell function and difficulties in using specific molecular markers to distinguish between subsets of myeloid cell populations. Here we review each of these concepts and include a discussion of future challenges that will need to be overcome to develop newer and improved immune modulatory therapies for the injured brain or spinal cord.
Topics: Animals; Cell Movement; Humans; Inflammation; Myeloid Cells; Spinal Cord Injuries
PubMed: 21400005
DOI: 10.1007/s13311-011-0032-6 -
Cytometry. Part a : the Journal of the... Apr 2012Currently, there is no standardized panel for immunophenotyping myeloid cells in mouse spleen using flow cytometry. Markers such as CD11b, CD11c, F4/80, Gr-1, Ly6C, and...
Currently, there is no standardized panel for immunophenotyping myeloid cells in mouse spleen using flow cytometry. Markers such as CD11b, CD11c, F4/80, Gr-1, Ly6C, and Ly6G have long been used to identify various splenic cell myeloid populations. Flow cytometry and fluorescence-activated cell sorting (FACS) analysis demonstrated that Ly6G/Ly6C markers are superior to Gr-1 for identifying splenic neutrophils, eosinophils, and subsets of monocytes/macrophages. Moreover, these experiments showed that F4/80 is not required for identifying these myeloid subsets and that many of the commercially available preparations of anti-F4/80 antibodies stain poorly for this antigen in spleen. Taken together, we have now developed an informative flow cytometry panel that can be combined with other cell markers to further delineate subpopulations of mouse splenic myeloid cells. This panel will be highly useful to investigators in the flow cytometry field, as there is a critical need to standardize the analysis of myeloid cell subsets.
Topics: Animals; Antigens, Ly; Biomarkers; Flow Cytometry; Immunophenotyping; Mice; Mice, Inbred C57BL; Myeloid Cells; Spleen
PubMed: 22213571
DOI: 10.1002/cyto.a.22012 -
Trends in Immunology Jan 2021The rapidly evolving area of immunometabolism has shed new light on the fundamental properties of products and intermediates of cellular metabolism (metabolites),... (Review)
Review
The rapidly evolving area of immunometabolism has shed new light on the fundamental properties of products and intermediates of cellular metabolism (metabolites), highlighting their key signaling roles in cell-to-cell communication. Recent evidence identifies the succinate-succinate receptor 1 (SUCNR1) axis as an essential regulator of tissue homeostasis. Succinate signaling via SUCNR1 guides divergent responses in immune cells, which are tissue and context dependent. Herein, we explore the main cellular pathways regulated by the succinate-SUCNR1 axis and focus on the biology of SUCNR1 and its roles influencing the function of myeloid cells. Hence, we identify new therapeutic targets and putative therapeutic approaches aimed at resolving detrimental myeloid cell responses in tissues, including those occurring in the persistently inflamed central nervous system (CNS).
Topics: Animals; Humans; Inflammation; Myeloid Cells; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 33279412
DOI: 10.1016/j.it.2020.11.004 -
Current Opinion in Immunology Feb 2013Molecules associated with dead or dying cells can be detected by receptors on macrophages and dendritic cells. Signals from these receptors impact myeloid cell function... (Review)
Review
Molecules associated with dead or dying cells can be detected by receptors on macrophages and dendritic cells. Signals from these receptors impact myeloid cell function and play a role in determining whether death is silent or proinflammatory, tolerogenic or immunogenic. Prominent among myeloid receptors detecting dead cells are C-type lectin receptors (CLRs). Signals from these receptors variably induce endocytosis of cell corpses, corpse degradation, retrieval of dead cell-associated antigens and/or modulation of immune responses. The sensing of tissue damage by myeloid CLRs complements detection of pathogens in immunity and represents an ancient response aimed at restoring tissue homeostasis.
Topics: Animals; Apoptosis; Autoantigens; Endocytosis; Homeostasis; Host-Pathogen Interactions; Humans; Immune Tolerance; Immunity, Innate; Immunomodulation; Lectins, C-Type; Myeloid Cells
PubMed: 23332826
DOI: 10.1016/j.coi.2012.12.007 -
Frontiers in Immunology 2023
Topics: Multiomics; Myeloid Cells; Myeloid Progenitor Cells
PubMed: 37799726
DOI: 10.3389/fimmu.2023.1292400 -
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 -
Transplantation Nov 2020
Topics: Allografts; Graft Rejection; Kidney Transplantation; Myeloid Cells
PubMed: 33122589
DOI: 10.1097/TP.0000000000003358