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Frontiers in Immunology 2020
Topics: Animals; Antigen Presentation; Dendritic Cells; Humans; Immune Tolerance
PubMed: 33117409
DOI: 10.3389/fimmu.2020.595841 -
International Review of Cell and... 2019Since their identification as the natural interferon-producing cell two decades ago, plasmacytoid dendritic cells (pDCs) have been attributed diverse functions in the... (Review)
Review
Since their identification as the natural interferon-producing cell two decades ago, plasmacytoid dendritic cells (pDCs) have been attributed diverse functions in the immune response. Their most well characterized function is innate, i.e., their rapid and robust production of type-I interferon (IFN-I) in response to viruses. However, pDCs have also been implicated in antigen presentation, activation of adaptive immune responses and immunoregulation. The mechanisms by which pDCs enact these diverse functions are poorly understood. One central debate is whether these functions are carried out by different pDC subpopulations or by plasticity in the pDC compartment. This chapter summarizes the latest reports regarding pDC function, heterogeneity, cell conversion and environmentally influenced plasticity, as well as the role of pDCs in infection, autoimmunity and cancer.
Topics: Animals; Cell Plasticity; Dendritic Cells; Humans
PubMed: 31759431
DOI: 10.1016/bs.ircmb.2019.10.002 -
Seminars in Immunopathology Feb 2017Dendritic cells (DC) are unique hematopoietic cells, linking innate and adaptive immune responses. In particular, they are considered as the most potent antigen... (Review)
Review
Dendritic cells (DC) are unique hematopoietic cells, linking innate and adaptive immune responses. In particular, they are considered as the most potent antigen presenting cells, governing both T cell immunity and tolerance. In view of their exceptional ability to present antigen and to interact with T cells, DC play distinct roles in shaping T cell development, differentiation and function. The outcome of the DC-T cell interaction is determined by the state of DC maturation, the type of DC subset, the cytokine microenvironment and the tissue location. Both regulatory T cells (Tregs) and DC are indispensable for maintaining central and peripheral tolerance. Over the past decade, accumulating data indicate that DC critically contribute to Treg differentiation and homeostasis.
Topics: Animals; Antigen Presentation; Autoimmune Diseases; Biomarkers; Cell Communication; Cell Differentiation; Dendritic Cells; Homeostasis; Humans; Immune Tolerance; Immunotherapy; Organ Specificity; Phenotype; Signal Transduction; T-Lymphocyte Subsets
PubMed: 27456849
DOI: 10.1007/s00281-016-0583-z -
International Review of Cell and... 2019Cancer immunotherapy harnesses the ability of the immune system to recognize and eliminate cancer. The potent ability of dendritic cells (DCs) to initiate and regulate... (Review)
Review
Cancer immunotherapy harnesses the ability of the immune system to recognize and eliminate cancer. The potent ability of dendritic cells (DCs) to initiate and regulate adaptive immune responses underpins the successful generation of anti-tumor immune responses. DCs are a heterogeneous leukocyte population comprised of distinct subsets that drive specific types of immune responses. Understanding how DCs induce tumor immune responses and the mechanisms adopted by tumors to evade DC surveillance is essential to render immunotherapies more effective. This review discusses current knowledge of the roles played by different DC subsets in human cancer and how these might be manipulated as new immunotherapeutics to improve CD8 T cell-mediated immune responses, with a particular focus on the conventional type 1 DCs (cDC1).
Topics: Animals; Cancer Vaccines; Dendritic Cells; Humans; Immunotherapy; Neoplasms
PubMed: 31810552
DOI: 10.1016/bs.ircmb.2019.07.006 -
Medical Microbiology and Immunology Aug 2020Dendritic cells (DCs) are a heterogeneous population of antigen-presenting cells that act to bridge innate and adaptive immunity. DCs are critical in mounting effective... (Review)
Review
Dendritic cells (DCs) are a heterogeneous population of antigen-presenting cells that act to bridge innate and adaptive immunity. DCs are critical in mounting effective immune responses to tissue damage, pathogens and cancer. Immature DCs continuously sample tissues and engulf antigens via endocytic pathways such as phagocytosis or macropinocytosis, which result in DC activation. Activated DCs undergo a maturation process by downregulating endocytosis and upregulating surface proteins controlling migration to lymphoid tissues where DC-mediated antigen presentation initiates adaptive immune responses. To traffic to lymphoid tissues, DCs must adapt their motility mechanisms to migrate within a wide variety of tissue types and cross barriers to enter lymphatics. All steps of DC migration involve cell-cell or cell-substrate interactions. This review discusses DC migration mechanisms in immunity and cancer with a focus on the role of cytoskeletal processes and cell surface proteins, including integrins, lectins and tetraspanins. Understanding the adapting molecular mechanisms controlling DC migration in immunity provides the basis for therapeutic interventions to dampen immune activation in autoimmunity, or to improve anti-tumour immune responses.
Topics: Animals; Antigen Presentation; Cell Communication; Cell Movement; Chemokines; Cytoskeleton; Dendritic Cells; Humans; Membrane Proteins; Mice; Neoplasms
PubMed: 32451606
DOI: 10.1007/s00430-020-00680-4 -
Cellular & Molecular Immunology Nov 2018Autophagy and immunity share the property of being auto-protective for the organism. Autophagy is an important degradation pathway that buffers nutrient deprivation by... (Review)
Review
Autophagy and immunity share the property of being auto-protective for the organism. Autophagy is an important degradation pathway that buffers nutrient deprivation by recycling macromolecules in organisms from yeast to man. Perturbations in autophagy are associated with inflammation and cancer development. Emerging studies have characterized the molecular details regarding how autophagy is controlled by immune cells. Among these, dendritic cells (DCs) are one of the most potent professional antigen-presenting cells critical for the activation of naïve T cells to maintain immune tolerance and drive protective immunity to infection and cancer. DCs undergo functional maturation that can either lead to an immunostimulatory phenotype, as in the context of infection, or to a tolerogenic phenotype associated with immunosuppression to self-antigens, as well as to cancer. An increasing number of recent studies has characterized the involvement of autophagy in DC functions in various physiological and pathological contexts. Here, we provide a comprehensive review of these outcomes and discuss the limitation of the models used and the forefront of the knowledge concerning the crosstalk between autophagy and DC biology.
Topics: Animals; Autophagy; Dendritic Cells; Humans; Immune Tolerance; Immunity, Cellular; T-Lymphocytes
PubMed: 29578531
DOI: 10.1038/cmi.2018.2 -
European Journal of Pharmacology Dec 2017Atherosclerosis is characterized by lipid accumulation and chronic inflammation of the arterial wall, involving both innate and adaptive immune responses. Accumulation... (Review)
Review
Atherosclerosis is characterized by lipid accumulation and chronic inflammation of the arterial wall, involving both innate and adaptive immune responses. Accumulation of lipid-laden macrophages is a key event in atherosclerosis. However, also other immune cells, such as dendritic cells (DC) and T cells, are found within lesions. DCs are classified as a separate lineage of mononuclear phagocytes that arise from progenitors distinct from precursors of monocytes/macrophages. Although a clear attribution of the effects of antigen-presenting cells (APCs) to monocytes/macrophages and DCs is hampered by the use of promiscuous surface markers, recent research has approached to resolve the contribution of bona fide DCs and their subsets, and of plasmacytoidDCs (pDCs) to atherosclerosis. We here discuss the pathogenic and protective mechanisms engaged by APCs in atherosclerosis and highlight current concepts to further address their role in atherosclerosis.
Topics: Animals; Atherosclerosis; Dendritic Cells; Humans
PubMed: 28822856
DOI: 10.1016/j.ejphar.2017.08.016 -
International Journal of Molecular... May 2016Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that play a critical role in the induction of antitumor immunity. Therefore, various strategies have... (Review)
Review
Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that play a critical role in the induction of antitumor immunity. Therefore, various strategies have been developed to deliver tumor-associated antigens (TAAs) to DCs as cancer vaccines. The fusion of DCs and whole tumor cells to generate DC-tumor fusion cells (DC-tumor FCs) is an alternative strategy to treat cancer patients. The cell fusion method allows DCs to be exposed to the broad array of TAAs originally expressed by whole tumor cells. DCs then process TAAs endogenously and present them through major histocompatibility complex (MHC) class I and II pathways in the context of costimulatory molecules, resulting in simultaneous activation of both CD4⁺ and CD8⁺ T cells. DC-tumor FCs require optimized enhanced immunogenicity of both DCs and whole tumor cells. In this context, an effective fusion strategy also needs to produce immunogenic DC-tumor FCs. We discuss the potential ability of DC-tumor FCs and the recent progress in improving clinical outcomes by DC-tumor FC-based cancer vaccines.
Topics: Animals; Antigens, Neoplasm; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cancer Vaccines; Cell Fusion; Dendritic Cells; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Humans; Lymphocyte Activation; Tumor Cells, Cultured
PubMed: 27240347
DOI: 10.3390/ijms17060828 -
Frontiers in Immunology 2019With the advent of combined immunotherapies, personalized dendritic cell (DC)-based vaccination could integrate the current standard of care for the treatment of a large... (Review)
Review
With the advent of combined immunotherapies, personalized dendritic cell (DC)-based vaccination could integrate the current standard of care for the treatment of a large variety of tumors. Due to their proficiency at antigen presentation, DC are key coordinators of the innate and adaptive immune system, and have critical roles in the induction of antitumor immunity. However, despite proven immunogenicity and favorable safety profiles, DC-based immunotherapies have not succeeded at inducing significant objective clinical responses. Emerging data suggest that the combination of DC-based vaccination with other cancer therapies may fully unleash the potential of DC-based cancer vaccines and improve patient survival. In this review, we discuss the recent efforts to develop innovative personalized DC-based vaccines and their use in combined therapies, with a particular focus on ovarian cancer and the promising results of mutanome-based personalized immunotherapies.
Topics: Cancer Vaccines; Dendritic Cells; Humans; Immunotherapy; Precision Medicine
PubMed: 31031762
DOI: 10.3389/fimmu.2019.00766 -
Journal of Reconstructive Microsurgery Oct 2018Dendritic cells (DCs) are bone marrow-derived, professional antigen-presenting cells with tolerogenic function. The ability of DCs to regulate alloantigen-specific T... (Review)
Review
BACKGROUND
Dendritic cells (DCs) are bone marrow-derived, professional antigen-presenting cells with tolerogenic function. The ability of DCs to regulate alloantigen-specific T cell responses and to promote tolerance has aligned them ideally for a role in vascularized composite allotransplantation (VCA). In this study, we summarize the current evidence for DC therapies for tolerance induction to alleviate the requirement for chronic immunosuppression.
METHOD
A comprehensive and structured review of manuscripts published on VCA was performed using the MEDLINE and PubMed databases. All eligible studies published from the year 2000 to 2017 were included in the final results.
RESULT
Nineteen original preclinical and clinical studies that employed cell therapy for VCA were included in this review. In vivo DC therapy was found to direct the alloimmune response toward either transplant rejection or tolerance in VCA models. While injection of mature DCs rapidly increases T-cell activity in humans and promotes transplant rejection, the injection of immature DCs acts as an immunosuppressant and inhibits T-cell activity. In addition to immature DCs, mesenchymal stem cells were also found to have a positive effect on allotransplantation of solid organs and bone marrow via cytokine expression which decreases the alloreactive effector lymphocytes and increases CD4+/CD25+/FoxP3 Tregs. Despite the promising findings, the efficacy of cell-based therapies varies greatly across studies, partly due to different methods of cell isolation and purification techniques, source, route and timing of administration, and combination immunosuppressive therapy.
CONCLUSION
Additional research is needed to evaluate the efficacy and safety of DC and other cell-based therapeutic measures in human allotransplant recipients. Future direction will focus on the development of novel methods to reduce immunosuppression and develop more individualized management, as well as the clinical application of basic research in the mechanisms of immunologic tolerance.
Topics: Animals; Cell Proliferation; Cell- and Tissue-Based Therapy; Dendritic Cells; Graft Survival; Humans; Immunosuppression Therapy; Models, Animal; Rats; Vascularized Composite Allotransplantation
PubMed: 29945289
DOI: 10.1055/s-0038-1661336