Search

Dendritic cells (DCs) are specialized antigen-presenting cells that are crucial for maintaining self-tolerance, initiating immune responses against pathogens, and patrolling body compartments. Despite promising aspects, DC-based immunotherapy faces challenges that include limited availability, immune escape in tumors, immunosuppression in the tumor microenvironment, and the need for effective combination therapies. A further limitation in DC-based immunotherapy is the low population of migratory DC (around 5%–10%) that migrate to lymph nodes (LNs) through afferent lymphatics depending on the LN draining site. By increasing the population of migratory DCs, DC-based immunotherapy could enhance immunotherapeutic effects on target diseases. This paper reviews the importance of DC migration and current research progress in the context of DC-based immunotherapy. [ABSTRACT FROM AUTHOR]

The ability of mesenchymal stromal cells (MSCs) to suppress immune responses combined with their potential to actively participate in tissue repair provides a strong rationale for the use of MSCs as a new treatment option in diseases characterized by inflammation and severe tissue damage, such as Crohn's disease (CD) and perianal fistulas. Multiple studies have shown that MSCs suppress a range of immune cells, such as dendritic cells (DC), naïve and effector T cells, and natural killer (NK) cells. Recently published papers attribute the immunosuppressive capacity of MSCs to soluble factors produced by MSCs, such as prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase (IDO). Promising results are obtained from phase I and II clinical trials with autologous and allogeneic MSCs as treatment for refractory CD and perianal fistulas; however the question remains: what are the molecular mechanisms underlying the immunomodulating properties of MSCs? This paper highlights the present knowledge on the immunosuppressive effects of MSCs and its complexity in relation to CD and perianal fistulas. [ABSTRACT FROM AUTHOR]

Various findings concerning the clinical significance of quantitative changes in hepatitis B surface antigen (HBsAg) during the acute and chronic phase of hepatitis B virus (HBV) infection have been reported. In addition to being a biomarker of HBV-replication activity, it has been reported that HBsAg could contribute to the immunopathogenesis of HBV persistent infection. Moreover, HBsAg could become an attractive target for immune therapy, since the cellular and humeral immune response against HBsAg might be able to control the HBV replication and life cycle. However, several reports have described the immune suppressive function of HBsAg. HBsAg might suppress monocytes, dendritic cells (DCs), natural killer (NK), and natural killer T (NK-T) cells by direct interaction. On the other hand, cytotoxic T lymphocytes (CTLs) and helper T (Th) cells were exhausted by high amounts of HBsAg. In this paper, we focused on the immunological aspects of HBsAg, since better understanding of the interaction between HBsAg and immune cells could contribute to the development of an immune therapy as well as a biomarker of the state of HBV persistent infection. [ABSTRACT FROM AUTHOR]

Despite variability, the majority of HIV-1-infected individuals progress to AIDS characterized by high viral load andmassive CD4+ T-cell depletion. However, there is a subset of HIV-1-positive individuals that does not progress and spontaneously maintains an undetectable viral load. This infrequent patient population is defined as HIV-1 controllers (HIV controllers), and represents less than 1% of HIV-1-infected patients. HIV-1-specific CD4+ T cells and the pool of central memory CD4+ T cells are also preserved despite immune activation due to HIV-1 infection. The majority of HIV controllers are also defined by the absence of massive CD4+ T-cell depletion, even after 10 years of infection. However, the mechanisms involved in protection against HIV-1 disease progression have not been elucidated yet. Controllers represent a heterogeneous population; we describe in this paper some common characteristics concerning innate immune response and CD4+ T cells of HIV controllers. [ABSTRACT FROM AUTHOR]

In 1999, two independent groups identified plasmacytoid dendritic cells (PDC) as major type I interferon- (IFN-) producing cells in the blood. Since then, evidence is accumulating that PDC are a multifunctional cell population effectively coordinating innate and adaptive immune responses. This paper focuses on the role of different immune cells and their interactions in the surveillance of alpha herpes virus infections, summarizes current knowledge on PDC surface receptors and their role in direct cell-cell contacts, and develops a risk factor model for the clinical implications of herpes simplex and varicella zoster virus reactivation. Data from studies involving knockout mice and cell-depletion experiments as well as human studies converge into a "spider web", in which the direct and indirect crosstalk between many cell populations tightly controls acute, latent, and recurrent alpha herpes virus infections. Notably, cells involved in innate immune regulations appear to shape adaptive immune responses more extensively than previously thought. [ABSTRACT FROM AUTHOR]

Background. Atherosclerosis is a chronic inflammatory disease with atherosclerotic plaques containing inflammatory infiltrates predominantly consisting of monocytes/macrophages and activated T cells. More recent is the implication of dendritic cells (DCs) in the disease. Since DCs were demonstrated in human arteries in 1995, numerous studies in humans suggest a role for these professional antigen-presenting cells in atherosclerosis. Aim. This paper focuses on the observations made in blood and arteries of patients with atherosclerosis. In principal, flow cytometric analyses show that circulating myeloid (m) and plasmacytoid (p) DCs are diminished in coronary artery disease, while immunohistochemical studies describe increased intimal DC counts with evolving plaque stages. Moreover, mDCs and pDCs appear to behave differently in atherosclerosis. Yet, the origin of plaque DCs and their relationship with blood DCs are unknown. Therefore, several explanations for the observed changes are postulated. In addition, the technical challenges and discrepancies in the research field are discussed. Future. Future studies in humans, in combination with experimental animal studies will unravel mechanisms leading to altered blood and plaque DCs in atherosclerosis. As DCs are crucial for inducing but also dampening immune responses, understanding their life cycle, trafficking and function in atherosclerosis will determine potential use of DCs in antiatherogenic therapies. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are the most potent antigen-presenting cells. They play a vital role in the initiation of immune response by presenting antigens to T cells and followed by induction of T-cell response. Reported research in animal studies indicated that vaccine immunity could be a promising alternative therapy for cancer patients. However, broad clinical utility has not been achieved yet, owing to the low transfection efficiency of DCs. Therefore, it is essential to improve the transfection efficiency of DC-based vaccination in immunotherapy. In several studies, DCs were genetically engineered by tumor-associated antigens or by immune molecules such as costimulatory molecules, cytokines, and chemokines. Encouraging results have been achieved in cancer treatment using various animal models. This paper describes the recent progress in gene delivery systems including viral vectors and nonviral carriers forDC-based genetically engineered vaccines. The reverse and three-dimensional transfection systems developed in DCs are also discussed. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that are critical for the generation of effective cytotoxic T lymphocyte (CTL) responses; however, their function and phenotype are often defective or altered in tumor-bearing hosts, which may limit their capacity to mount an effective tumor-specific CTL response. In particular, the manner in which exogenous tumor antigens are acquired, processed, and cross-presented to CD8 T cells by DCs in tumor-bearing hosts is not well understood, but may have a profound effect on antitumor immunity. In this paper, we have examined the role of DCs in the cross-presentation of tumor antigen in terms of their subset, function, migration, and location with the intention of examining the early processes that contribute to the development of an ineffective anti-tumor immune response. [ABSTRACT FROM AUTHOR]

The goal of cancer vaccines is to induce antitumor immunity that ultimately will reduce tumor burden in tumor environment. Several strategies involving dendritic cells- (DCs)- based vaccine incorporating different tumor-associated antigens to induce antitumor immune responses against tumors have been tested in clinical trials worldwide. Although DCs-based vaccine such as fusions of whole tumor cells and DCs has been proven to be clinically safe and is efficient to enhance antitumor immune responses for inducing effective immune response and for breaking T-cell tolerance to tumor-associated antigens (TAAs), only a limited success has occurred in clinical trials. This paper reviews tumor immune escape and current strategies employed in the field of tumor/DC fusions vaccine aimed at enhancing activation of TAAs-specific cytotoxic T cells in tumor microenvironment. [ABSTRACT FROM AUTHOR]