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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 -
Frontiers in Immunology 2021Dendritic cells (DC) are antigen-presenting cells that can communicate with T cells both directly and indirectly, regulating our adaptive immune responses against... (Review)
Review
Dendritic cells (DC) are antigen-presenting cells that can communicate with T cells both directly and indirectly, regulating our adaptive immune responses against environmental and self-antigens. Under some microenvironmental conditions DC develop into anti-inflammatory cells which can induce immunologic tolerance. A substantial body of literature has confirmed that in such settings regulatory DC (DCreg) induce T cell tolerance by suppression of effector T cells as well as by induction of regulatory T cells (Treg). Many studies have been undertaken with human DCreg which, as a surrogate marker of antigen-specific tolerogenic potential, only poorly activate allogeneic T cell responses. Fewer studies have addressed the abilities of, or mechanisms by which these human DCreg suppress autologous effector T cell responses and induce infectious tolerance-promoting Treg responses. Moreover, the agents and properties that render DC as tolerogenic are many and varied, as are the cells' relative regulatory activities and mechanisms of action. Herein we review the most current human and, where gaps exist, murine DCreg literature that addresses the cellular and molecular biology of these cells. We also address the clinical relevance of human DCreg, highlighting the outcomes of pre-clinical mouse and non-human primate studies and early phase clinical trials that have been undertaken, as well as the impact of innate immune receptors and symbiotic microbial signaling on the immunobiology of DCreg.
Topics: Animals; Cell- and Tissue-Based Therapy; Clinical Trials as Topic; Dendritic Cells; Disease Models, Animal; Humans; Immune System Diseases; Immune Tolerance; Mice; Primates; T-Lymphocytes, Regulatory
PubMed: 33777019
DOI: 10.3389/fimmu.2021.633436 -
Nature Nanotechnology May 2022
Topics: Cancer Vaccines; Dendritic Cells; Immunotherapy; Nanoparticles
PubMed: 35410370
DOI: 10.1038/s41565-022-01089-1 -
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 -
Current Opinion in Immunology Jun 2023Dendritic cells (DCs) are ubiquitous immune cells endowed with a unique capacity to initiate antigen-specific immunity and tolerance. Owing to their unique functional... (Review)
Review
Dendritic cells (DCs) are ubiquitous immune cells endowed with a unique capacity to initiate antigen-specific immunity and tolerance. Owing to their unique functional attributes, DCs have long been considered ideal candidates for the induction of effective antitumour responses. At the forefront of the cancer-immunity cycle, attempts to harness DC natural adjuvant properties in the clinic have resulted so far in suboptimal antitumour responses. A better understanding of the heterogeneity of the DC network and its dynamics within the tumour microenvironment will provide a blueprint to fully capitalise on their functional properties to achieve more effective antitumour responses. In this review, we will briefly summarise the origin and heterogeneity of the DC network, their roles in shaping antitumour immunity and in modulating the response to immune checkpoint blockade therapies.
Topics: Humans; Neoplasms; Immunotherapy; Dendritic Cells; Tumor Microenvironment
PubMed: 37236040
DOI: 10.1016/j.coi.2023.102341 -
Biomedicine & Pharmacotherapy =... Jun 2023Breast cancer (BC) is the most common cancer in women worldwide. Although substantial progress has been made in the diagnosis and treatment of breast cancer, the... (Review)
Review
Breast cancer (BC) is the most common cancer in women worldwide. Although substantial progress has been made in the diagnosis and treatment of breast cancer, the efficacy and side effects of traditional treatment methods are still unsatisfactory. In recent years, immunotherapy including tumor vaccine has achieved great success in the treatment of BC. Dendritic cells (DCs) are multifunctional antigen-presenting cells that play an important role in the initiation and regulation of innate and adaptive immune responses. Numerous studies have shown that DC-based treatments might have a potential effect on BC. Among them, the clinical study of DC vaccine in BC has demonstrated considerable anti-tumor effect, and some DC vaccines have entered the stage of clinical trials. In this review, we summarize the immunomodulatory effects and related mechanisms of DC vaccine in breast cancer as well as the progress of clinical trials to propose possible challenges of DC vaccines and new development directions.
Topics: Humans; Female; Breast Neoplasms; Immunotherapy; Immunity; Dendritic Cells; Cancer Vaccines
PubMed: 37058818
DOI: 10.1016/j.biopha.2023.114685 -
International Review of Cell and... 2021Dendritic cells (DC) and macrophages (Mϕ) constitute the most abundant antigen presenting cells in the human intestinal mucosa. In resting conditions, they are... (Review)
Review
Dendritic cells (DC) and macrophages (Mϕ) constitute the most abundant antigen presenting cells in the human intestinal mucosa. In resting conditions, they are essential to maintain the mechanisms of immune tolerance toward food antigens and commensals, at the time that they keep the capacity to initiate and maintain antigen-specific pro-inflammatory immune responses toward invading pathogens. Nevertheless, this delicate equilibrium between immunity and tolerance is not perfect, like in coeliac disease (CD), where DC and Mϕ drive the development of antigen-specific immune responses toward dietary gluten peptides. In this review, we provide therefore a comprehensive discussion about CD pathogenesis, the human intestinal immune system and the biology of intestinal DC and Mϕ both in resting conditions and in CD. Last, but not least, we discuss about all the remaining issues pending to be studied regarding DC and Mϕ contribution toward CD pathogenesis. This may allow the identification of unique and specific factors which may be useful in the clinical practice, as well as identify new therapeutic targets in order to reestablish the loss intestinal homeostasis in CD.
Topics: Animals; Celiac Disease; Dendritic Cells; Humans; Immune Tolerance; Immunity, Innate; Intestines; Macrophages
PubMed: 33707058
DOI: 10.1016/bs.ircmb.2020.09.006 -
Frontiers in Immunology 2024Dendritic cells (DCs) play a central role in the orchestration of effective T cell responses against tumors. However, their functional behavior is context-dependent. DC... (Review)
Review
Dendritic cells (DCs) play a central role in the orchestration of effective T cell responses against tumors. However, their functional behavior is context-dependent. DC type, transcriptional program, location, intratumoral factors, and inflammatory milieu all impact DCs with regard to promoting or inhibiting tumor immunity. The following review introduces important facets of DC function, and how subset and phenotype can affect the interplay of DCs with other factors in the tumor microenvironment. It will also discuss how current cancer treatment relies on DC function, and survey the myriad ways with which immune therapy can more directly harness DCs to enact antitumor cytotoxicity.
Topics: Humans; Dendritic Cells; Neoplasms; Tumor Microenvironment; Immunotherapy; Animals
PubMed: 38903502
DOI: 10.3389/fimmu.2024.1393451 -
Frontiers in Immunology 2022To gain access to the brain, a so-called immune-privileged organ due to its physical separation from the blood stream, pathogens and particularly viruses have been... (Review)
Review
To gain access to the brain, a so-called immune-privileged organ due to its physical separation from the blood stream, pathogens and particularly viruses have been selected throughout evolution for their use of specific mechanisms. They can enter the central nervous system through direct infection of nerves or cerebral barriers or through cell-mediated transport. Indeed, peripheral lymphoid and myeloid immune cells can interact with the blood-brain and the blood-cerebrospinal fluid barriers and allow viral brain access using the "Trojan horse" mechanism. Among immune cells, at the frontier between innate and adaptive immune responses, dendritic cells (DCs) can be pathogen carriers, regulate or exacerbate antiviral responses and neuroinflammation, and therefore be involved in viral transmission and spread. In this review, we highlight an important contribution of DCs in the development and the consequences of viral brain infections.
Topics: Brain; Central Nervous System; Dendritic Cells; Humans; Myeloid Cells; Virus Diseases
PubMed: 35529884
DOI: 10.3389/fimmu.2022.862053 -
Advanced Science (Weinheim,... Nov 2023Spleen and lymphoid organs are important targets for messenger RNA (mRNA) delivery in various applications. Current nanoparticle delivery methods rely on drainage to...
Spleen and lymphoid organs are important targets for messenger RNA (mRNA) delivery in various applications. Current nanoparticle delivery methods rely on drainage to lymph nodes from intramuscular or subcutaneous injections. In difficult-to-transfect antigen-presenting cells (APCs), such as dendritic cells (DCs), effective mRNA transfection remains a significant challenge. In this study, a lymphatic targeting carrier using DC membranes is developed, that efficiently migrated to lymphoid organs, such as the spleen and lymph nodes. The nanoparticles contained an ionizable lipid (YK009), which ensured a high encapsulation efficacy of mRNA and assisted mRNA with endosomal escape after cellular uptake. Dendritic cell-mimicking nanoparticles (DCMNPs) showed efficient protein expression in both the spleen and lymph nodes after intramuscular injections. Moreover, in immunized mice, DCMNP vaccination elicited Spike-specific IgG antibodies, neutralizing antibodies, and Th1-biased SARS-CoV-2-specific cellular immunity. This work presents a powerful vaccine formula using DCMNPs, which represents a promising vaccine candidate for further research and development.
Topics: Mice; Animals; Dendritic Cells; RNA, Messenger; Nanoparticles; Immunity, Cellular; Vaccines
PubMed: 37867227
DOI: 10.1002/advs.202302423