scholarly journals Understanding Dendritic Cells and Their Role in Cutaneous Carcinoma and Cancer Immunotherapy

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Valerie R. Yanofsky ◽  
Hiroshi Mitsui ◽  
Diane Felsen ◽  
John A. Carucci

Dendritic cells (DC) represent a diverse group of professional antigen-presenting cells that serve to link the innate and adaptive immune systems. Their capacity to initiate a robust and antigen-specific immune response has made them the ideal candidates for cancer immunotherapies. To date, the clinical impact of DC immunotherapy has been limited, which may, in part, be explained by the complex nature of DC biology. Multiple distinct subsets of DCs have been identified in the skin, where they can be broadly subcategorized into epidermal Langerhans cells (LC), myeloid-derived dermal dendritic cells (mDC) and plasmacytoid dendritic cells (pDC). Each subset is functionally unique and may activate alternate branches of the immune system. This may be relevant for the treatment of squamous cell carcinoma, where we have shown that the tumor microenvironment may preferentially suppress the activity of mDCs, while LCs remain potent stimulators of immunity. Here, we provide an in depth analysis of DC biology, with a particular focus on skin DCs and their role in cutaneous carcinoma. We further explore the current approaches to DC immunotherapy and provide evidence for the targeting of LCs as a promising new strategy in the treatment of skin cancer.

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yonghong Yang ◽  
Huan Dou ◽  
Xiaoqin Li ◽  
Yuxian Song ◽  
Wei Gong ◽  
...  

Dendritic cells (DCs), as the most potent professional antigen presenting cells, play a crucial role in both innate and adaptive immune systems. Genomic bacterial DNA mimicked by unmethylated CpG motifs is discovered to possess immunostimulatory effects. CpG-DNA recognized by Toll-like receptor 9 (TLR9) on DCs arouses many immune diseases (such as cancer, viral infection, and autoimmune disorders). In this study we investigated the effects of FC-98 on CpG-induced bone marrow-derived DCs (BMDCs). The results showed that FC-98 significantly inhibited the CpG-induced BMDCs maturation and function by suppressing the expression of surface markers (CD40, CD80, CD86, and MHCII). Moreover, FC-98 downregulated the expression of C-X-C motif chemokine 10 (CXCL-10) both at the mRNA and protein level after CpG induction. Meanwhile, FC-98 markedly affected the migration of BMDCs to T cells without affecting their endocytosis capacity. Furthermore, FC-98 was confirmed to decrease CXCL-10 expression by inhibiting CpG-induced activation of MAPKs (ERK, JNK, and p38) and STAT1 signaling. Overall, these results suggested that FC-98 was a potential molecule in the treatment of CXCL-10-mediated immune diseases.


Author(s):  
Lucie Kratochvílová ◽  
Petr Sláma

This article is an overview of dendritic cells (DCs) in cattle. The understanding of the immune system and the role of DCs in many ways can contribute to their use in the prevention and treatment of many infectious and autoimmune diseases. DCs are bone marrow-derived cells that function as professional antigen presenting cells. They act as messengers between the innate and the adaptive immune systems. The morphology of DCs results in a very large surface to volume ratio. That is, the DCs have a very large surface area compared to the overall cell volume. Currently, most dendritic cells research occurs in the human and mice. There is a lack of studies in cattle describing DCs. DCs survey the body and collect information relevant to the immune system. They are then able to instruct and direct the adaptive arms to respond to challenges.


2019 ◽  
Vol 5 (1) ◽  
pp. eaav0216 ◽  
Author(s):  
Mohammad Arifuzzaman ◽  
Yuvon R. Mobley ◽  
Hae Woong Choi ◽  
Pradeep Bist ◽  
Cristina A. Salinas ◽  
...  

Mast cells (MCs) are strategically distributed at barrier sites and prestore various immunocyte-recruiting cytokines, making them ideal targets for selective activation to treat peripheral infections. Here, we report that topical treatment with mastoparan, a peptide MC activator (MCA), enhances clearance ofStaphylococcus aureusfrom infected mouse skins and accelerates healing of dermonecrotic lesions. Mastoparan functions by activating connective tissue MCs (CTMCs) via the MRGPRX2 (Mas-related G protein-coupled receptor member X2) receptor. Peripheral CTMC activation, in turn, enhances recruitment of bacteria-clearing neutrophils and wound-healing CD301b+dendritic cells. Consistent with MCs playing a master coordinating role, MC activation also augmented migration of various antigen-presenting dendritic cells to draining lymph nodes, leading to stronger protection against a second infection challenge. MCAs therefore orchestrate both the innate and adaptive immune arms, which could potentially be applied to combat peripheral infections by a broad range of pathogens.


Author(s):  
KANCHAN K. MISHRA ◽  
SUMIT BHARADVA ◽  
MEGHNAD G. JOSHI ◽  
ARVIND GULBAKE

Dendritic cells (DCs) play a critical role in the regulation of adaptive immune responses, furthermore they act as a bridge between the innate and the adaptive immune systems they have been ideal candidates for cell-based immunotherapy of cancers and infections in humans. The first reported trial using DCs in 1995, since they have been used in trials all over the world for several of indications, including cancer and human immunodeficiency virus infection. Generally, for in vitro experiments or for DCs vaccination monocyte-derived dendritic cells (moDCs) were generated from purified monocytes that isolated from peripheral blood by density gradient centrifugation. A variety of methods can be used for enrichment of monocytes for generation of clinical-grade DCs. Herein we summarized up to date understanding of systems and inputs used in procedures to differentiate DCs from blood monocytes in vitro.


2020 ◽  
Vol 49 (D1) ◽  
pp. D630-D638
Author(s):  
Jiawei Wang ◽  
Wei Dai ◽  
Jiahui Li ◽  
Qi Li ◽  
Ruopeng Xie ◽  
...  

Abstract Anti-CRISPR (Acr) proteins naturally inhibit CRISPR-Cas adaptive immune systems across bacterial and archaeal domains of life. This emerging field has caused a paradigm shift in the way we think about the CRISPR-Cas system, and promises a number of useful applications from gene editing to phage therapy. As the number of verified and predicted Acrs rapidly expands, few online resources have been developed to deal with this wealth of information. To overcome this shortcoming, we developed AcrHub, an integrative database to provide an all-in-one solution for investigating, predicting and mapping Acr proteins. AcrHub catalogs 339 non-redundant experimentally validated Acrs and over 70 000 predicted Acrs extracted from genome sequence data from a diverse range of prokaryotic organisms and their viruses. It integrates state-of-the-art predictors to predict potential Acrs, and incorporates three analytical modules: similarity analysis, phylogenetic analysis and homology network analysis, to analyze their relationships with known Acrs. By interconnecting all modules as a platform, AcrHub presents enriched and in-depth analysis of known and potential Acrs and therefore provides new and exciting insights into the future of Acr discovery and validation. AcrHub is freely available at http://pacrispr.erc.monash.edu/AcrHub/.


2009 ◽  
Vol 68 (3) ◽  
pp. 300-304 ◽  
Author(s):  
A Tournadre ◽  
P Miossec

This review focuses on the contribution of the local production of chemokines and cytokines and of dendritic cells (DC) to the pathogenesis of inflammatory myopathies. DC are the most efficient professional antigen-presenting cells (APC), which are critical for the development of innate and adaptive immune responses. Chemokines are important mediators of the immune response as they regulate leucocyte recruitment to tissue and play a key role in inflammatory diseases by acting on T-cell and DC migration. Recent advances indicate that the muscle cell itself could participate in the inflammatory process. Furthermore, the T-helper (Th) type 1 and Th17 proinflammatory cytokines, present in myositis samples, are associated with the migration, differentiation and maturation of inflammatory cells and allow a network of interactions between all the components of the immune response. An understanding of such interactions is essential because it can lead to therapeutic applications.


Author(s):  
Soi-Cheng Law ◽  
Pascale Wehr ◽  
Harriet Purvis ◽  
Ranjeny Thomas

Dendritic cells (DCs) are specialized antigen-presenting cells which link the innate and adaptive immune responses, activating and priming effector CD4+ T cells, cross-presenting antigen to CD8+ T cells, and promoting B-cell antibody production. DCs also play important roles in the maintenance of immune tolerance. DCs and T cells underpin the basis of the autoimmune response in rheumatoid arthritis. In this chapter we describe the function of DCs and the response of T cells in rheumatoid arthritis pathogenesis, introduce the DC and T-cell players and their function in the immune system, then review the evidence for their involvement in the pathogenesis of rheumatoid arthritis (RA), particularly through the presentation of antigen that triggers the differentiation of autoreactive T cells, as well as innate immune effector functions. Finally, the emerging prospects for DC targeting for immunotherapy are covered.


2017 ◽  
Vol 312 (3) ◽  
pp. H368-H374 ◽  
Author(s):  
Kala B. Dixon ◽  
Sean S. Davies ◽  
Annet Kirabo

Hypertension is the major risk factor for morbidity and mortality from myocardial infarction, stroke, heart failure, and chronic kidney disease. Despite its importance, the pathogenesis of essential hypertension is poorly understood. During the past several years, it has become evident that T cells contribute to hypertension. Activated T cells accumulate in the perivascular space and the kidney and release cytokines that promote vascular dysfunction and end-organ damage. Although dendritic cells play a pivotal role in initiating adaptive immune responses, T cells have taken center stage in studies implicating the immune system in the genesis of hypertension. The mechanisms by which T cells are activated and the antigens involved are poorly understood. We recently showed that hypertension is associated with increased dendritic cell production of the TH17 polarizing cytokines, IL-6, IL-1β, and IL-23. This occurs in part by increased superoxide production via NADPH oxidase and protein modification by highly reactive isolevuglandins (IsoLGs). IsoLGs are produced via the isoprostane pathway of free radical-mediated lipid peroxidation and, when adducted to proteins, have the potential to act as neoantigens. In this review, we discuss recent advances in our understanding of the role of antigen-presenting dendritic cells in the pathophysiology of hypertension and highlight potential neoantigens that may contribute to this disease.


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Matteo Bordignon ◽  
Paola Rottoli ◽  
Carlo Agostini ◽  
Mauro Alaibac

Sarcoidosis is a multisystemic inflammatory disorder with cutaneous lesions present in about one-quarter of the patients. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of nonnecrotizing epithelial cell granulomas on histologic studies. The development and progression of specific cutaneous sarcoidosis involves a complex interaction between cells of the adaptive immune systems, notably T-lymphocytes and dendritic cells. In this paper, we will discuss the role of T-cells and skin dendritic cells in the development of primary cutaneous sarcoidosis and comment on the potential antigenic stimuli that may account for the development of the immunological response. We will further explore the contributions of selected cytokines to the immunopathological process. The knowledge of the adaptive immunological mechanisms operative in cutaneous sarcoidosis may subsequently be useful for identifying prevention and treatment strategies of systemic sarcoidosis.


2006 ◽  
Vol 74 (8) ◽  
pp. 4624-4633 ◽  
Author(s):  
Maureen L. Drakes ◽  
Steven J. Czinn ◽  
Thomas G. Blanchard

ABSTRACT Helicobacter infections are present in approximately 50% of humans, causing severe illnesses such as gastritis and malignancies. Dendritic cells (DC) are critical antigen-presenting cells which link innate and adaptive immune responses. The mechanism of dendritic cell regulation in Helicobacter-induced gastritis is poorly understood. These studies characterized DC isolated from the lamina propria of Helicobacter-infected mice and analyzed innate and adaptive immune responses elicited by Helicobacter antigen (Ag)-pulsed DC. The presence of DC was elevated in the gastric lamina propria infiltrate of infected mice in comparison with controls. After treatment with Helicobacter felis Ag, DC were polarized to secrete interleukin-6 as the dominant cytokine. In the presence of DC and Helicobacter Ag, responder allogeneic T cells in culture exhibited limited cell division. We suggest that the response of DC and T cells to Helicobacter Ag is critical to the chronic persistence of Helicobacter-induced gastritis.


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