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Background: Dendritic cells (DCs) comprise heterogeneous populations of cells, which act as central orchestrators of the immune response. Applicability of primary DCs is restricted due to their scarcity and therefore DC models are commonly employed in DC-based immunotherapy strategies and in vitro tests assessing DC function. However, the interrelationship between the individual in vitro DC models and their relative resemblance to specific primary DC populations remain elusive. Objective: To describe and assess functionality and applicability of the available in vitro DC models by using a genome-wide transcriptional approach. Methods: Transcriptional profiling was performed with four commonly used in vitro DC models (MUTZ-3-DCs, monocyte-derived DCs, CD34-derived DCs and Langerhans cells (LCs)) and nine primary DC populations (dermal DCs, LCs, blood and tonsillar CD123+, CD1c+and CD141+DCs, and blood CD16+DCs). Results: Principal Component Analysis showed that transcriptional profiles of each in vitro DC model most closely resembled CD1c+and CD141+tonsillar myeloid DCs (mDCs) among primary DC populations. Thus, additional differentiation factors may be required to generate model DCs that more closely resemble other primary DC populations. Also, no model DC stood out in terms of primary DC resemblance. Nevertheless, hierarchical clustering showed clusters of differentially expressed genes among individual DC models as well as primary DC populations. Furthermore, model DCs were shown to differentially express immunologically relevant transcripts and transcriptional signatures identified for each model DC included several immune-associated transcripts. Conclusion: The unique transcriptional profiles of in vitro DC models suggest distinct functionality in immune applications. The presented results will aid in the selection of an appropriate DC model for in vitro assays and assist development of DC-based immunotherapy. [ABSTRACT FROM AUTHOR]

CD1d-restricted invariant natural killer T cells (iNKT) constitute an important immunoregulatory T-cell subset involved in the induction of antitumor immune responses. Here, we provide a view on the recent observation that Vγ9Vδ2-T cells, through trogocytosis of CD1d-containing membrane fragments, have the capacity to act as antigen presenting cells for iNKT. [ABSTRACT FROM AUTHOR]

Improvement of patient survival by anti-angiogenic therapy has proven limited. A vaccination approach inducing an immune response against the tumor vasculature combines the benefits of immunotherapy and anti-angiogenesis, and may overcome the limitations of current anti-angiogenic drugs. Strategies to use whole endothelial cell vaccines and DNA- or protein vaccines against key players in the VEGF signaling axis, as well as specific markers of tumor endothelial cells, have been tested in preclinical studies. Current clinical trials are now testing the promise of this specific anti-cancer vaccination approach. This review will highlight the state-of-the-art in this exciting field of cancer research. [ABSTRACT FROM AUTHOR]

ATP-binding cassette (ABC) transporters are known for their involvement in clinical multidrug resistance (MDR) and their physiological defensive functions in barrier organs. More recently, attention has been focused on their possible involvement in the regulation of immune responses following the identification of their substrates as known immunomodulating agents (e.g. prostaglandins, leukotrienes and cyclic nucleotides) and their functional expression in various immune effector cells, most notably in dendritic cells (DCs). This review addresses the possible roles of ABC transporters in DC development and function, as well as the putative immunostimulatory potential of their cytostatic substrates and how this knowledge might benefit DC-based chemo-immunotherapies. [Copyright &y& Elsevier]

Abstract: Dendritic cell (DC) migration to draining lymph nodes is important for the initiation of an effective immune response. Recently we reported that the human ATP-binding cassette (ABC) transporter multidrug resistance protein 4 (MRP4 and ABCC4) is required for the migration of human DC. Since the ABC transporter MRP1 (ABCC1) was previously shown to play a role in both human and mouse DC migration, we here studied whether Mrp4 is similarly required for DC migration in mice and whether the absence of Mrp4 interferes with the generation of an immune response. Immunological responses were compared in wild-type FVB (FVBwt), FVB Mrp4 knockout (KO) or FVB Mrp4/5 double knockout (dKO) mice. Skin, a preferred immunization site, was analyzed for DC markers, as well as for Mrp1 and Mrp4 expression. Whereas Mrp1 was abundantly present within FVBwt skin, only few Mrp4 expressing cells were detected. In addition, no Mrp4 protein expression was detected on in vitro cultured FVBwt bone marrow-derived DC (BM-DC). DC migration from murine ear skin was unaltered between FVBwt and MRP4/5 dKO animals. The absence of Mrp4 also had no effect on immune responses upon allergen sensitization, immunization or oral tolerance induction. We thus conclude that in contrast to its human counterpart, murine Mrp4 is not involved in DC migration, nor indeed, in the generation of an effective immune response. These data reveal disparities in the physiological role of ABC transporters between species, which may derive from differences in substrate specificity. [Copyright &y& Elsevier]