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Frontiers in Immunology 2020Despite significant advances in the field of cancer immunotherapy, the majority of patients still do not benefit from treatment and must rely on traditional therapies.... (Review)
Review
Despite significant advances in the field of cancer immunotherapy, the majority of patients still do not benefit from treatment and must rely on traditional therapies. Dendritic cells have long been a focus of cancer immunotherapy due to their role in inducing protective adaptive immunity, but cancer vaccines have shown limited efficacy in the past. With the advent of immune checkpoint blockade and the ability to identify patient-specific neoantigens, new vaccines, and combinatorial therapies are being evaluated in the clinic. Dendritic cells are also emerging as critical regulators of the immune response within tumors. Understanding how to augment the function of these intratumoral dendritic cells could offer new approaches to enhance immunotherapy, in addition to improving the cytotoxic and targeted therapies that are partially dependent upon a robust immune response for their efficacy. Here we will discuss the role of specific dendritic cell subsets in regulating the anti-tumor immune response, as well as the current status of dendritic cell-based immunotherapies, in order to provide an overview for future lines of research and clinical trials.
Topics: Animals; Antineoplastic Agents, Immunological; Cancer Vaccines; Dendritic Cells; Humans; Immune Checkpoint Inhibitors; Immunotherapy, Adoptive; Neoplasms; Phenotype; Signal Transduction; Treatment Outcome
PubMed: 32508825
DOI: 10.3389/fimmu.2020.00924 -
Cellular & Molecular Immunology Jun 2020Dendritic cells are powerful antigen-presenting cells that are essential for the priming of T cell responses. In addition to providing T-cell-receptor ligands and... (Review)
Review
Dendritic cells are powerful antigen-presenting cells that are essential for the priming of T cell responses. In addition to providing T-cell-receptor ligands and co-stimulatory molecules for naive T cell activation and expansion, dendritic cells are thought to also provide signals for the differentiation of CD4+ T cells into effector T cell populations. The mechanisms by which dendritic cells are able to adapt and respond to the great variety of infectious stimuli they are confronted with, and prime an appropriate CD4+ T cell response, are only partly understood. It is known that in the steady-state dendritic cells are highly heterogenous both in phenotype and transcriptional profile, and that this variability is dependent on developmental lineage, maturation stage, and the tissue environment in which dendritic cells are located. Exposure to infectious agents interfaces with this pre-existing heterogeneity by providing ligands for pattern-recognition and toll-like receptors that are variably expressed on different dendritic cell subsets, and elicit production of cytokines and chemokines to support innate cell activation and drive T cell differentiation. Here we review current information on dendritic cell biology, their heterogeneity, and the properties of different dendritic cell subsets. We then consider the signals required for the development of different types of Th immune responses, and the cellular and molecular evidence implicating different subsets of dendritic cells in providing such signals. We outline how dendritic cell subsets tailor their response according to the infectious agent, and how such transcriptional plasticity enables them to drive different types of immune responses.
Topics: Animals; Antigen Presentation; Cell Differentiation; Dendritic Cells; Humans; Models, Biological; T-Lymphocytes, Helper-Inducer; Transcription, Genetic
PubMed: 32433540
DOI: 10.1038/s41423-020-0465-0 -
The Journal of Experimental Medicine Jan 2021Dendritic cells (DCs) contribute a small fraction of the tumor microenvironment but are emerging as an essential antitumor component based on their ability to foster T... (Review)
Review
Dendritic cells (DCs) contribute a small fraction of the tumor microenvironment but are emerging as an essential antitumor component based on their ability to foster T cell immunity and immunotherapy responses. Here, we discuss our expanding view of DC heterogeneity in human tumors, as revealed with meta-analysis of single-cell transcriptome profiling studies. We further examine tumor-infiltrating DC states that are conserved across patients, cancer types, and species and consider the fundamental and clinical relevance of these findings. Finally, we provide an outlook on research opportunities to further explore mechanisms governing tumor-infiltrating DC behavior and functions.
Topics: Dendritic Cells; Gene Expression Profiling; Humans; Neoplasms; Tumor Microenvironment
PubMed: 33601412
DOI: 10.1084/jem.20200264 -
Methods in Molecular Biology (Clifton,... 2019Dendritic cells are a specialized type of antigen-presenting cell that bridges both innate and adaptive immune system function. While much is understood about dendritic...
Dendritic cells are a specialized type of antigen-presenting cell that bridges both innate and adaptive immune system function. While much is understood about dendritic cells and their role in the immune system, the study of these cells is critical to gain a more complete understanding of their function. The isolation and culture of dendritic cells from mouse tissues can be challenging, due in part to the low number of cells isolated. The following protocol outlines methods to optimize the isolation and culture of large numbers of dendritic cells from mouse bone marrow to facilitate a broad range of downstream experimental applications.
Topics: Animals; Bone Marrow Cells; Cell Differentiation; Dendritic Cells; Granulocyte-Macrophage Colony-Stimulating Factor; Mice
PubMed: 30798520
DOI: 10.1007/978-1-4939-9167-9_4 -
Nature Communications Jun 2022Immunogenic cell death significantly contributes to the success of anti-cancer therapies, but immunogenicity of different cell death modalities widely varies....
Immunogenic cell death significantly contributes to the success of anti-cancer therapies, but immunogenicity of different cell death modalities widely varies. Ferroptosis, a form of cell death that is characterized by iron accumulation and lipid peroxidation, has not yet been fully evaluated from this perspective. Here we present an inducible model of ferroptosis, distinguishing three phases in the process-'initial' associated with lipid peroxidation, 'intermediate' correlated with ATP release and 'terminal' recognized by HMGB1 release and loss of plasma membrane integrity-that serves as tool to study immune cell responses to ferroptotic cancer cells. Co-culturing ferroptotic cancer cells with dendritic cells (DC), reveals that 'initial' ferroptotic cells decrease maturation of DC, are poorly engulfed, and dampen antigen cross-presentation. DC loaded with ferroptotic, in contrast to necroptotic, cancer cells fail to protect against tumor growth. Adding ferroptotic cancer cells to immunogenic apoptotic cells dramatically reduces their prophylactic vaccination potential. Our study thus shows that ferroptosis negatively impacts antigen presenting cells and hence the adaptive immune response, which might hinder therapeutic applications of ferroptosis induction.
Topics: Cell Death; Dendritic Cells; Ferroptosis; Humans; Lipid Peroxidation; Neoplasms
PubMed: 35760796
DOI: 10.1038/s41467-022-31218-2 -
Trends in Immunology Jan 2021Dendritic cells (DCs), the most efficient antigen-presenting cells, are necessary for the effective activation of naïve T cells. DCs can also acquire tolerogenic... (Review)
Review
Dendritic cells (DCs), the most efficient antigen-presenting cells, are necessary for the effective activation of naïve T cells. DCs can also acquire tolerogenic functions in vivo and in vitro in response to various stimuli, including interleukin (IL)-10, transforming growth factor (TGF)-β, vitamin D3, corticosteroids, and rapamycin. In this review, we provide a wide perspective on the regulatory mechanisms, including crosstalk with other cell types, downstream signaling pathways, transcription factors, and epigenetics, underlying the acquisition of tolerogenesis by DCs, with a special focus on human studies. Finally, we present clinical assays targeting, or based on, tolerogenic DCs in inflammatory diseases. Our discussion provides a useful resource for better understanding the biology of tolerogenic DCs and their manipulation to improve the immunological fitness of patients with certain inflammatory conditions.
Topics: Autoimmunity; Dendritic Cells; Humans; Immune Tolerance; Inflammation; Signal Transduction; T-Lymphocytes
PubMed: 33293219
DOI: 10.1016/j.it.2020.11.001 -
Life Sciences Aug 2020Dendritic cells (DCs) are considered as professional antigen presenting cells (APCs), containing a variety of subsets, that can be resident in organs or migrating among... (Review)
Review
Dendritic cells (DCs) are considered as professional antigen presenting cells (APCs), containing a variety of subsets, that can be resident in organs or migrating among the lymphoid and non-lymphoid organs. In a normal steady condition, DCs concomitantly process and present antigens on major histocompatibility complex (MHC) class I and II. However, they are further activated after exposing to antigens. Recently, several approaches have been exerted to improve antigen presentation potency, to elicit powerful immune responses against tumor cells. In DC-based cancer immunotherapy, DC is obtained from patient and modulated ex vivo in order to entice the immune system toward tumor elimination. Several approaches have been on the evaluation for long-term anti-tumor immune responses by DCs. On the other side, combination of DC vaccines with other cancer therapies, like chemotherapy and monoclonal antibodies could confer efficient cancer therapeutics. In this review article, we first go through the immunobiology of DC, and development of DC vaccines. Then, we concentrate on the DC immunotherapy by highlighting combinational approaches to enhance the efficacy of cancer treatment strategies.
Topics: Adjuvants, Immunologic; Antigen Presentation; Combined Modality Therapy; Dendritic Cells; Humans; Immunotherapy; Neoplasms; Radiotherapy; Tumor Microenvironment
PubMed: 32205087
DOI: 10.1016/j.lfs.2020.117580 -
Frontiers in Immunology 2018Dendritic cells (DC) are professional antigen presenting cells, uniquely able to induce naïve T cell activation and effector differentiation. They are, likewise,... (Review)
Review
Dendritic cells (DC) are professional antigen presenting cells, uniquely able to induce naïve T cell activation and effector differentiation. They are, likewise, involved in the induction and maintenance of immune tolerance in homeostatic conditions. Their phenotypic and functional heterogeneity points to their great plasticity and ability to modulate, according to their microenvironment, the acquired immune response and, at the same time, makes their precise classification complex and frequently subject to reviews and improvement. This review will present general aspects of the DC physiology and classification and will address their potential and actual uses in the management of human disease, more specifically cancer, as therapeutic and monitoring tools. New combination treatments with the participation of DC will be also discussed.
Topics: Animals; Biomarkers; Cancer Vaccines; Cell Differentiation; Combined Modality Therapy; Dendritic Cells; Humans; Immune System; Immune System Phenomena; Immunotherapy; Neoplasms; Phenotype; Treatment Outcome; Tumor Microenvironment
PubMed: 30719026
DOI: 10.3389/fimmu.2018.03176 -
International Journal of Molecular... Feb 2023Dendritic cells (DCs) are acknowledged as the most potent professional antigen-presenting cells (APCs), able to induce adaptive immunity and support the innate immune...
Dendritic cells (DCs) are acknowledged as the most potent professional antigen-presenting cells (APCs), able to induce adaptive immunity and support the innate immune response [...].
Topics: Humans; Dendritic Cells; Adaptive Immunity; Immunity, Innate; Neoplasms
PubMed: 36835665
DOI: 10.3390/ijms24044253 -
Pathologie (Heidelberg, Germany) Aug 2022Histiocytic and dendritic cell neoplasms (HDCNs) represent very rare tumors, which have been the subject of debate during the last few years. (Review)
Review
BACKGROUND
Histiocytic and dendritic cell neoplasms (HDCNs) represent very rare tumors, which have been the subject of debate during the last few years.
OBJECTIVES
We aimed to provide a comprehensive review of the subject.
MATERIALS AND METHODS
The experience gained by the authors in large international studies and as a national reference center has been summarized to highlight the characteristics of each entity.
RESULTS
The clinical, morphologic, phenotypic, and molecular data of the different entities included under the heading of HDCNs are extensively discussed.
CONCLUSION
Currently, HDCNs are classified in the group of orphan diseases for which a standardized therapy is lacking. An international registry would facilitate expansion and dissemination of knowledge of these diseases and improve their treatment.
Topics: Dendritic Cells; Histiocytes; Neoplasms
PubMed: 36175665
DOI: 10.1007/s00292-022-01116-x