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Advances in Cancer Research 2004Several lines of evidence from recent years support the existence of cancer immunosurveillance, especially studies of natural killer (NK) cells and the IFN-gamma... (Review)
Review
Several lines of evidence from recent years support the existence of cancer immunosurveillance, especially studies of natural killer (NK) cells and the IFN-gamma pathway. However, immune suppression is clearly observed in cancer patients and tumor-bearing animals as well. The fact is that although cancers often elicit a vigorous immune response during the early part of their growth, the immune response is soon down-regulated, permitting progressive tumor growth. Apparently, the intrinsic plasticity of tumors allows the immune system to sculpt the immunogenic phenotypes of tumors to escape efficient immune destruction. But most evidently, several mechanisms have now been found to contribute to the failure of immune control of tumor growth. Tumor cells have a very low level of MHC class II, costimulatory molecules, and weak antigens. They also produce immune suppressive factors (VEGF, IL-10, PGE(2)) that exert systemic effects on immune cell function. In particular, disabled dendritic cell differentiation, maturation, migration, and function are fundamental to this defect, as they are the most potent antigen-presenting cells (APCs) of the immune system, interacting with T and B lymphocyte as well as NK cells to induce and modulate immune responses. In addition, tumors also alter host hematopoiesis and produce large numbers of immature dendritic cells, and evidence shows that these cells are directly immune suppressive. Harnessing the immune system for effective cancer therapy has remained a great challenge. DC-based vaccines, or DC-based vaccines in combination with treatments designed to improve the host immune environment, may offer hope for more effective cancer immunotherapy. Tumor-host interactions are an important determinant of tumor behavior and response to therapy. How tumors interact with their hosts is thus a very broad and complex topic. In this chapter, we will focus on tumor-host immune interactions and the roles of dendritic cell dysfunction in tumor avoidance of host immune responses. We will survey recent findings regarding tumor immune surveillance, antitumor host immune responses, and how the immune system also functions to promote or select tumor variants with reduced immunogenicity. We will then discuss immune suppression caused by tumors, which is clearly observed in tumor-bearing animals and cancer patients. Finally, we will discuss altered dendritic cell function and differentiation in some detail, as it is likely to be one of the most fundamental mechanisms by which tumors escape immune responses.
Topics: Animals; Cell Differentiation; Dendritic Cells; Humans; Immune Tolerance; Immunologic Surveillance; Neoplasms; Tumor Escape
PubMed: 15530555
DOI: 10.1016/S0065-230X(04)92002-7 -
Seminars in Immunology Aug 2005
Topics: Animals; Cell Differentiation; Dendritic Cells
PubMed: 15955711
DOI: 10.1016/j.smim.2005.05.014 -
Journal of Dermatological Science May 1998Before the establishment of procedures to cultured dendritic cells (DCs) from peripheral blood or bone marrow progenitor cells using a combination of several cytokines,... (Review)
Review
Dendritic cell activation induced by various stimuli, e.g. exposure to microorganisms, their products, cytokines, and simple chemicals as well as adhesion to extracellular matrix.
Before the establishment of procedures to cultured dendritic cells (DCs) from peripheral blood or bone marrow progenitor cells using a combination of several cytokines, Langerhans cells (LCs) of the epidermis have been used as the best characterized dendritic cell population. The studies using LCs freshly isolated from the skin or DCs from the blood or spleen and cultured DCs from progenitors have elucidated that although DCs are a unique cell population characterized by their potent antigen presenting function, especially by their induction of primary antigen-specific T cell responses, they are immature and less potent in antigen presenting function immediately after isolated from the skin or from other non-lymphoid tissues. Therefore, DCs must be stimulated to augment their antigen presenting function and to initiate a naive T cell response. Recently, it becomes clear that a variety of signals, such as microorganisms, cytokines, adhesion to extracellular matrix, and simple chemicals like haptens, can induce this activation process in DCs, which is also called as DC maturation. In this paper, we discuss what kinds of stimuli effectively activate DCs.
Topics: Animals; Cell Adhesion; Cytokines; Dendritic Cells; Extracellular Matrix; Humans
PubMed: 10342743
DOI: 10.1016/s0923-1811(99)00005-5 -
Medecine Sciences : M/S Jan 2014Dendritic cells are a rare and heterogeneous population of professional antigen-presenting cells. Several murine dendritic cell subpopulations have been identified that... (Review)
Review
Dendritic cells are a rare and heterogeneous population of professional antigen-presenting cells. Several murine dendritic cell subpopulations have been identified that differ in their phenotype and functional properties. In the steady state, committed dendritic cell precursors differentiate into lymphoid organ-resident dendritic cells and migratory tissue dendritic cells. During inflammation appears an additional dendritic cell subpopulation that has been termed « inflammatory dendritic cells ». Inflammatory dendritic cells differentiate in situ from monocytes recruited to the site of inflammation. Here, we discuss how mouse inflammatory dendritic cells differ from macrophages and from other dendritic cell populations. Finally, we review recent work on human inflammatory dendritic cells.
Topics: Animals; Cell Differentiation; Dendritic Cells; Humans; Inflammation; Lymphocyte Activation; Mice; Monocytes; T-Lymphocytes
PubMed: 24472461
DOI: 10.1051/medsci/20143001015 -
Expert Reviews in Molecular Medicine Nov 2008Dendritic cells are the most potent antigen-presenting cells of the mammalian immune system and are central to the initiation and maintenance of the adaptive immune... (Review)
Review
Dendritic cells are the most potent antigen-presenting cells of the mammalian immune system and are central to the initiation and maintenance of the adaptive immune response. They are crucial for the presentation of antigen to T cells and B cells, as well as the induction of chemokines and proinflammatory cytokines, which orchestrate the balance of the cell-mediated (Th1) and antibody (Th2) response. This ability of dendritic cells to present antigen and release chemokines and cytokines also bridges the innate and adaptive immune responses by driving T cell activation. These cells thus possess key immunological functions that make them the front line of defence for the targeting and clearance of any invading pathogen and, as such, they underpin the host immune response to infection. For efficient infection, invading pathogens often need to overcome these sentinel immune functions. It is therefore not surprising that pathogens have evolved numerous mechanisms to target dendritic cell functions directly or indirectly during infection, and at least one herpesvirus--human cytomegalovirus--has evolved a life cycle that hijacks dendritic cells for its long-term persistence in the infected host.
Topics: Antigen Presentation; Cytomegalovirus; Dendritic Cells; Host-Pathogen Interactions; Humans; Models, Biological; T-Lymphocytes
PubMed: 19025715
DOI: 10.1017/S1462399408000872 -
Immunobiology 2006Dendritic cells and macrophages are major components of the phagocyte system and are professional antigen presenting cells. In the current review, we discuss the... (Review)
Review
Dendritic cells and macrophages are major components of the phagocyte system and are professional antigen presenting cells. In the current review, we discuss the differential contribution of dendritic cell and macrophage subsets in the clearance of dying cells and the consequences of these processes. We hypothesize that under steady-state conditions, the clearance of apoptotic cells is mostly confined to a specialized subset of phagocytes with anti-inflammatory properties.
Topics: Animals; Apoptosis; Dendritic Cells; Humans; Macrophages; Necrosis; Phagocytosis
PubMed: 16920495
DOI: 10.1016/j.imbio.2006.05.023 -
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue Apr 2019Severe trauma or massive deep burn can cause significant immunosuppression associated with sepsis and multiple organ failure. Dendritic cell (DC), as the professional... (Review)
Review
Severe trauma or massive deep burn can cause significant immunosuppression associated with sepsis and multiple organ failure. Dendritic cell (DC), as the professional antigen presenting cells and activating factor of immune response, plays an extraordinary role in initiating and regulating congenital and adaptive immune response. The quantity, functional changes, relevant molecular mechanisms and reverse measures of DC after trauma/burn were reviewed in order to intensively study the changes of DC after trauma/burn and provide a reference for exploring effective intervention measures for trauma/burn.
Topics: Adaptive Immunity; Burns; Dendritic Cells; Humans; Multiple Organ Failure; Sepsis; Trauma Severity Indices
PubMed: 31109429
DOI: 10.3760/cma.j.issn.2095-4352.2019.04.025 -
Mucosal Immunology Nov 2008Dendritic cells (DCs) are a heterogenous population of antigen-presenting cells, of which conventional DCs and plasmacytoid DCs are the main subsets. Like DC subsets in... (Review)
Review
Dendritic cells (DCs) are a heterogenous population of antigen-presenting cells, of which conventional DCs and plasmacytoid DCs are the main subsets. Like DC subsets in the central lymphoid organs, DC subsets in the lungs exert specific functions that can be associated with distinct expression of endocytic receptors, cell-surface molecules, and anatomical location within the lung. In recent years, DC populations are increasingly split up into a seemingly endless number of defined sub-populations. We argue that this is not a "stamp-collecting" activity but essential for a deeper understanding of the immune response to pathogens like respiratory viruses or tolerance to harmless antigens. In homeostatic conditions, a fine-tuned balance exists between the various functions of lung DC subsets, which is necessary for maintaining immune homeostasis in the lung. However, infectious or inflammatory conditions can profoundly alter the functions of steady-state DC subsets and recruit inflammatory type DCs to the lung. This might be important for clearing the inflicting pathogenic stimulus, but could at the same time also be involved in causing immune pathology.
Topics: Animals; Antigens; Asthma; Dendritic Cells; Humans; Lung; Respiratory Tract Infections
PubMed: 19079211
DOI: 10.1038/mi.2008.39 -
International Review of Cytology 2000Dendritic cells (DC) are bone-marrow-derived cells that function as professional antigen-presenting cells (APC). Liver is an essential organ for a host defense. It not... (Review)
Review
Dendritic cells (DC) are bone-marrow-derived cells that function as professional antigen-presenting cells (APC). Liver is an essential organ for a host defense. It not only is armed with a powerful macrophage system but also is constantly surveyed by a heavy traffic of DC and lymphocytes. In case of emergency, such as infection and inflammation, DC traffic in the liver is accelerated. DC in the liver (interstitial DC) capture and process antigens, enter the draining lymph (DC in hepatic lymph) and accumulate in the T-cell area of hepatic lymph nodes (LN). DC in the LN present antigens to T and B cells to initiate immune responses. In accelerated states, DC precursors are recruited to the liver and soon translocate to hepatic lymph. Even mature lymph DC can undergo a blood-lymph translocation from the liver to hepatic LN after i.v. injection into normal rats. Rat Kupffer cells in the hepatic sinusoids are capable of selectively trapping DC from the blood in vivo and in vitro, suggesting involvement of certain adhesion molecules. Kupffer cells presumably elaborate chemokines to attract and trap the recruited DC via selective adhesion, leading to DC extravasation. The accelerated traffic and the presence of blood-lymph translocation would induce rapid and efficient immune responses and thus contribute to the local defense to antigens within liver tissues as well as systemic defense to blood-borne antigens. DC progenitors are also present in the liver, and these may play an important role in tolerance induction in liver transplantation.
Topics: Animals; Dendritic Cells; Humans; Liver; Lymph
PubMed: 10761116
DOI: 10.1016/s0074-7696(00)97003-7 -
Current Opinion in Hematology May 2002Hematopoietic growth factors have made it possible to collect, manufacture, and engineer dendritic cells ex vivo for clinical use and expand dendritic cell subsets in... (Review)
Review
Hematopoietic growth factors have made it possible to collect, manufacture, and engineer dendritic cells ex vivo for clinical use and expand dendritic cell subsets in vivo when administered to patients. Dendritic cells are important vectors in the induction of an effective immune response against infection and neoplastic disease. Antigens alone, even those preprocessed to bind to antigen-presenting major histocompatibility complex class I and II molecules, are insufficient to regulate effective T-cell-mediated immunity. Activated dendritic cells are essential to this task. Studies of dendritic cell biology in the laboratory and preclinical studies have facilitated the implementation of clinical trials using dendritic cells in the treatment of melanoma and other cancers. Dendritic cell subset functional differences, effective tumor target antigen loading of dendritic cells for presentation to immune effector cells, dendritic cell maturation, the route of dendritic cell administration to humans, and immunologic monitoring are parameters that require vigorous study in the context of dendritic cell immunotherapy of cancer.
Topics: Animals; Cancer Vaccines; Dendritic Cells; Hematopoietic Cell Growth Factors; Humans; Neoplasms
PubMed: 11953665
DOI: 10.1097/00062752-200205000-00005