Human dendritic cell subsets.
TL;DR: Comparative studies are now allowing many of these properties of Dendritic cells to be more fully understood in the context of human immunology.
Abstract: Dendritic cells are highly adapted to their role of presenting antigen and directing immune responses. Developmental studies indicate that DCs originate independently from monocytes and tissue macrophages. Emerging evidence also suggests that distinct subsets of DCs have intrinsic differences that lead to functional specialisation in the generation of immunity. Comparative studies are now allowing many of these properties to be more fully understood in the context of human immunology.
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TL;DR: Cross-talk between cancer cells and the proximal immune cells ultimately results in an environment that fosters tumor growth and metastasis, and understanding the nature of this dialog will allow for improved therapeutics that simultaneously target multiple components of the TME, increasing the likelihood of favorable patient outcomes.
Abstract: Cancer development and progression occurs in concert with alterations in the surrounding stroma. Cancer cells can functionally sculpt their microenvironment through the secretion of various cytokines, chemokines, and other factors. This results in a reprogramming of the surrounding cells, enabling them to play a determinative role in tumor survival and progression. Immune cells are important constituents of the tumor stroma and critically take part in this process. Growing evidence suggests that the innate immune cells (macrophages, neutrophils, dendritic cells, innate lymphoid cells, myeloid-derived suppressor cells, and natural killer cells) as well as adaptive immune cells (T cells and B cells) contribute to tumor progression when present in the tumor microenvironment (TME). Cross-talk between cancer cells and the proximal immune cells ultimately results in an environment that fosters tumor growth and metastasis. Understanding the nature of this dialog will allow for improved therapeutics that simultaneously target multiple components of the TME, increasing the likelihood of favorable patient outcomes.
1,418 citations
Additional excerpts
...CD115, CD107b, FceRI, CD80, CD86 Antitumor (19, 95, 97, 99, 100)...
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01 Jan 2010
TL;DR: The data demonstrate a role for CD141+ DCs in the induction of cytotoxic T lymphocyte responses and suggest that they may be the most relevant targets for vaccination against cancers, viruses, and other pathogens.
Abstract: The characterization of human dendritic cell (DC) subsets is essential for the design of new vaccines. We report the first detailed functional analysis of the human CD141(+) DC subset. CD141(+) DCs are found in human lymph nodes, bone marrow, tonsil, and blood, and the latter proved to be the best source of highly purified cells for functional analysis. They are characterized by high expression of toll-like receptor 3, production of IL-12p70 and IFN-beta, and superior capacity to induce T helper 1 cell responses, when compared with the more commonly studied CD1c(+) DC subset. Polyinosine-polycytidylic acid (poly I:C)-activated CD141(+) DCs have a superior capacity to cross-present soluble protein antigen (Ag) to CD8(+) cytotoxic T lymphocytes than poly I:C-activated CD1c(+) DCs. Importantly, CD141(+) DCs, but not CD1c(+) DCs, were endowed with the capacity to cross-present viral Ag after their uptake of necrotic virus-infected cells. These findings establish the CD141(+) DC subset as an important functionally distinct human DC subtype with characteristics similar to those of the mouse CD8 alpha(+) DC subset. The data demonstrate a role for CD141(+) DCs in the induction of cytotoxic T lymphocyte responses and suggest that they may be the most relevant targets for vaccination against cancers, viruses, and other pathogens.
859 citations
Université Paris-Saclay1, University of Toronto2, Karolinska University Hospital3, Pierre-and-Marie-Curie University4, Cincinnati Children's Hospital Medical Center5, Memorial Sloan Kettering Cancer Center6, Paris Descartes University7, Necker-Enfants Malades Hospital8, University of Texas MD Anderson Cancer Center9, Icahn School of Medicine at Mount Sinai10, University of Pittsburgh11, Harvard University12, Brigham and Women's Hospital13, Mayo Clinic14
TL;DR: This revised classification system consists of 5 groups of diseases: (1) Langerhans-related, (2) cutaneous and mucocutaneous, and (3) malignant histiocytoses as well as (4) Rosai-Dorfman disease and (5) hemophagocytic lymphohistiocyts and macrophage activation syndrome.
848 citations
TL;DR: A universal toolbox for the automated identification of DCs through unsupervised analysis of conventional flow cytometry and mass cytometry data obtained from multiple mouse, macaque, and human tissues is provided and validated.
607 citations
Cites background from "Human dendritic cell subsets."
...Distinguishing DCs from Macs in human tissues has been equally challenging (Collin et al., 2013; McGovern et al., 2015)....
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TL;DR: What has been learned thus far about human DC biology from clinical studies are discussed, and how current approaches to apply DC vaccines in the clinic could be improved to enhance anti-tumor immunity are discussed.
Abstract: Immunotherapy using dendritic cell (DC)-based vaccination is an approved approach for harnessing the potential of a patient's own immune system to eliminate tumor cells in metastatic hormone-refractory cancer. Overall, although many DC vaccines have been tested in the clinic and proven to be immunogenic, and in some cases associated with clinical outcome, there remains no consensus on how to manufacture DC vaccines. In this review we will discuss what has been learned thus far about human DC biology from clinical studies, and how current approaches to apply DC vaccines in the clinic could be improved to enhance anti-tumor immunity.
495 citations
References
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TL;DR: Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge and are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.
Abstract: Interferons (IFNs) are the most important cytokines in antiviral immune responses. “Natural IFN-producing cells” (IPCs) in human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated and further characterized because of their rarity, rapid apoptosis, and lack of lineage markers. Purified IPCs are here shown to be the CD4+CD11c− type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge. pDC2s are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.
2,328 citations
University of Leicester1, Université de Montréal2, Burnet Institute3, French Institute of Health and Medical Research4, Centre national de la recherche scientifique5, University of Giessen6, Erasmus University Medical Center7, University of Texas MD Anderson Cancer Center8, University of Oxford9, Icahn School of Medicine at Mount Sinai10, Ludwig Maximilian University of Munich11, Miltenyi Biotec12, Walter and Eliza Hall Institute of Medical Research13, University of Brescia14, Jagiellonian University Medical College15, John Radcliffe Hospital16, University of Würzburg17
TL;DR: The present document proposes a nomenclature for monocytes and defines 3 types of monocytes (classical, intermediate, and nonclassical monocytes) and3 types of dendritic cells (plasmacytoid and 2 types of myeloid dendrites) in human and in mouse blood.
2,111 citations
TL;DR: Large numbers of DC progenitors are observed in cord blood and in adult blood from healthy donors, which should facilitate future studies of their Fc epsilon RI and CD4 receptors, and their use in stimulating T cell-mediated resistance to viruses and tumors.
Abstract: CD34+ cells in human cord blood and marrow are known to give rise to dendritic cells (DC), as well as to other myeloid lineages. CD34+ cells are rare in adult blood, however, making it difficult to use CD34+ cells to ascertain if DC progenitors are present in the circulation and if blood can be a starting point to obtain large numbers of these immunostimulatory antigen-presenting cells for clinical studies. A systematic search for DC progenitors was therefore carried out in several contexts. In each case, we looked initially for the distinctive proliferating aggregates that were described previously in mice. In cord blood, it was only necessary to deplete erythroid progenitors, and add granulocyte/macrophage colony-stimulating factor (GM-CSF) together with tumor necrosis factor (TNF), to observe many aggregates and the production of typical DC progeny. In adult blood from patients receiving CSFs after chemotherapy for malignancy, GM-CSF and TNF likewise generated characteristic DCs from HLA-DR negative precursors. However, in adult blood from healthy donors, the above approaches only generated small DC aggregates which then seemed to become monocytes. When interleukin 4 was used to suppress monocyte development (Jansen, J. H., G.-J. H. M. Wientjens, W. E. Fibbe, R. Willemze, and H. C. Kluin-Nelemans. 1989. J. Exp. Med. 170:577.), the addition of GM-CSF led to the formation of large proliferating DC aggregates and within 5-7 d, many nonproliferating progeny, about 3-8 million cells per 40 ml of blood. The progeny had a characteristic morphology and surface composition (e.g., abundant HLA-DR and accessory molecules for cell-mediated immunity) and were potent stimulators of quiescent T cells. Therefore, large numbers of DCs can be mobilized by specific cytokines from progenitors in the blood stream. These relatively large numbers of DC progeny should facilitate future studies of their Fc epsilon RI and CD4 receptors, and their use in stimulating T cell-mediated resistance to viruses and tumors.
1,993 citations
TL;DR: A negative feedback loop from the mature T helper cells may selectively inhibit prolonged TH1 or TH2 responses by regulating survival of the appropriate dendritic cell subset.
Abstract: It is not known whether subsets of dendritic cells provide different cytokine microenvironments that determine the differentiation of either type-1 T helper (T H 1) or T H 2 cells. Human monocyte (pDC1)–derived dendritic cells (DC1) were found to induce T H 1 differentiation, whereas dendritic cells (DC2) derived from CD4 + CD3 – CD11c – plasmacytoid cells (pDC2) induced T H 2 differentiation by use of a mechanism unaffected by interleukin-4 (IL-4) or IL-12. The T H 2 cytokine IL-4 enhanced DC1 maturation and killed pDC2, an effect potentiated by IL-10 but blocked by CD40 ligand and interferon-γ. Thus, a negative feedback loop from the mature T helper cells may selectively inhibit prolonged T H 1 or T H 2 responses by regulating survival of the appropriate dendritic cell subset.
1,967 citations
TL;DR: Results, with the distinct cell phenotype, indicate that plasmacytoid monocytes represent a specialized cell lineage that enters inflamed lymph nodes at high endothelial venules, where it produces type I interferon.
Abstract: We have identified two cell subsets in human blood based on the lack of lineage markers (lin-) and the differential expression of immunoglobulin-like transcript receptor 1 (ILT1) and ILT3. One subset (lin-/ILT3+/ILT1+) is related to myeloid dendritic cells. The other subset (lin-/ILT3+/ILT1+) corresponds to 'plasmacytoid monocytes'. These cells are found in inflamed lymph nodes in and around the high endothelial venules. They express CD62L and CXCR3, and produce extremely large amounts of type I interferon after stimulation with influenza virus or CD40L. These results, with the distinct cell phenotype, indicate that plasmacytoid monocytes represent a specialized cell lineage that enters inflamed lymph nodes at high endothelial venules, where it produces type I interferon. Plasmacytoid monocytes may protect other cells from viral infections and promote survival of antigen-activated T cells.
1,791 citations