المؤلفون: Walther, Romy, Wehner, Rebekka, Tunger, Antje, Julius, Ulrich, Schatz, Ulrike, Tselmin, Sergey, Bornstein, Stefan R., Schmitz, Marc, Graessler, Juergen

مصطلحات موضوعية: atherosclerosis, lipoprotein apheresis, monocytes, NK cells, T cells, Atherosklerose, Lipoprotein-Apherese, Monozyten, NK-Zellen, T-Zellen, info:eu-repo/classification/ddc/610, ddc:610

الوصف: Background: Atherosclerosis is considered a chronic inflammation of arterial vessels with the involvement of several immune cells causing severe cardiovascular diseases. Lipoprotein apheresis (LA) improves cardiovascular conditions of patients with severely disturbed lipid metabolism. In this context, little is known about the impact of LA on various immune cell populations, especially over time. Methods: Immune cells of 18 LA-naïve patients starting weekly LA treatment were analyzed before and after four apheresis cycles over the course of 24 weeks by flow cytometry. Results and Conclusions: An acute lowering effect of LA on T cell and natural killer (NK) cell subpopulations expressing CD69 was observed. The nonclassical and intermediate monocyte subsets as well as HLA-DR+ 6-sulfo LacNAc+ monocytes were significantly reduced during the apheresis procedure. We conclude that LA has the capacity to alter various immune cell subsets. However, LA has mainly short-term effects than long-term consequences on proportions of immune cells.

الإتاحة: https://tud.qucosa.de/id/qucosa%3A91977Test
https://tud.qucosa.de/api/qucosa%3A91977/attachment/ATT-0Test/

المؤلفون: Plesca, Ioana, Müller, Luise, Böttcher, Jan P., Medyouf, Hind, Wehner, Rebekka, Schmitz, Marc

مصطلحات موضوعية: Conventional dendritic cells, Monocyte-derived dendritic cells, Plasmacytoid dendritic cells, Tumor immunotherapy, Tumor microenvironment, Konventionelle dendritische Zellen, von Monozyten abgeleitete dendritische Zellen, plasmazytoide dendritische Zellen, Tumor-Immuntherapie, Tumor-Mikroumgebung, info:eu-repo/classification/ddc/610, ddc:610

الوصف: DCs play a pivotal role in orchestrating innate and adaptive antitumor immunity. Activated DCs can produce large amounts of various proinflammatory cytokines, initiate T-cell responses, and exhibit direct cytotoxicity against tumor cells. They also efficiently enhance the antitumoral properties of NK cells and T lymphocytes. Based on these capabilities, immunogenic DCs promote tumor elimination and are associated with improved survival of patients. Furthermore, they can essentially contribute to the clinical efficacy of immunotherapeutic strategies for cancer patients. However, depending on their intrinsic properties and the tumor microenvironment, DCs can be rendered dysfunctional and mediate tolerance by producing immunosuppressive cytokines and activating Treg cells. Such tolerogenic DCs can foster tumor progression and are linked to poor prognosis of patients. Here, we focus on recent studies exploring the phenotype, functional orientation, and clinical relevance of tumor-infiltrating conventional DC1, conventional DC2, plasmacytoid DCs, and monocyte-derived DCs in translational and clinical settings. In addition, recent findings demonstrating the influence of DCs on the efficacy of immunotherapeutic strategies are summarized.

العلاقة: info:eu-repo/grantAgreement/Bavaria International Junior Research Group/Elite Network/N-LW-2016-370/; info:eu-repo/grantAgreement/Deutsche Forschungsgemeinschaft/Inverses kamerabasiertes Weitfeld-Fluoreszenzmikroskop/442405234/; info:eu-repo/grantAgreement/Deutsche Forschungsgemeinschaft/Konfokales Laser Scanning Mikroskop mit Spektraler Detektion und FLIM/424926990/; info:eu-repo/grantAgreement/Deutsche Forschungsgemeinschaft/Die Rolle von cDC1 Heterogenität für die Immunantwort gegen Krebs/449174900/; info:eu-repo/grantAgreement/Deutsche Forschungsgemeinschaft/SPP 2306: Ferroptose: Von der Grundlagenforschung zur klinischen Anwendung/461704785//Die Rolle des ferroptotischen Zelltods für die Regulation der anti-tumor Immunität durch dendritische Zellen

الإتاحة: https://tud.qucosa.de/id/qucosa%3A91352Test
https://tud.qucosa.de/api/qucosa%3A91352/attachment/ATT-0Test/

المؤلفون: Krüger, Thomas, Wehner, Rebekka, Herbig, Maik, Kräter, Martin, Kramer, Michael, Middeke, Jan Moritz, Stölzel, Friedrich, List, Catrin, Egger-Heidrich, Katharina, Teipel, Raphael, Oelschlägel, Uta, Wermke, Martin, Jambor, Helena, Wobus, Manja, Schetelig, Johannes, Jöhrens, Korinna, Tonn, Torsten, Subburayalu, Julien, Schmitz, Marc, Bornhauser, Martin, Bonin, Malte von

مصطلحات موضوعية: mesenchymal stromal cells, allogeneic hematopoietic stem cell transplantation, graft-versus-host-disease, alloreactivity, bone marrow niche, mesenchymale Stromazellen, allogene hämatopoetische Stammzelltransplantation, Transplantat-gegen-Wirt-Krankheit, Alloreaktivität, Knochenmark-Nische, info:eu-repo/classification/ddc/610, ddc:610

الوصف: Functional impairment of the bone marrow (BM) niche has been suggested as a major reason for prolonged cytopenia and secondary graft failure after allogeneic hematopoietic cell transplantation (alloHCT). Because mesenchymal stromal cells (MSCs) serve as multipotent progenitors for several niche components in the BM, they might play a key role in this process. We used collagenase digested trephine biopsies to directly quantify MSCs in 73 patients before (n = 18) and/or after alloHCT (n = 65). For the first time, we demonstrate that acute graft-versus-host disease (aGvHD, n = 39) is associated with a significant decrease in MSC numbers. MSC reduction can be observed even before the clinical onset of aGvHD (n = 10). Assessing MSCs instantly after biopsy collection revealed phenotypic and functional differences depending on the occurrence of aGvHD. These differences vanished during ex vivo expansion. The MSC endotypes observed revealed an enhanced population of donor-derived classical dendritic cells type 1 and alloreactive T cells as the causing agent for compartmental inflammation and MSC damage before clinical onset of aGvHD was ascertained. In conclusion, MSCs endotypes may constitute a predisposing conductor of alloreactivity after alloHCT preceding the clinical diagnosis of aGvHD.

العلاقة: 1005554; info:eu-repo/grantAgreement/Deutsche Forschungsgemeinschaft/SPP 2127: Gen- und Zellbasierte Therapien für die Behandlung neuroretinaler Degeneration/399422891/

الإتاحة: https://tud.qucosa.de/id/qucosa%3A91411Test
https://tud.qucosa.de/api/qucosa%3A91411/attachment/ATT-0Test/

المؤلفون: Mentrup, Torben, Stumpff-Niggemann, Anna Yamina, Leinung, Nadja, Schlosser, Christine, Schubert, Katja, Wehner, Rebekka, Tunger, Antje, Schatz, Valentin, Neubert, Patrick, Gradtke, Ann-Christine, Wolf, Janina, Rose-John, Stefan, Saftig, Paul, Dalpke, Alexander, Jantsch, Jonathan, Schmitz, Marc, Fluhrer, Regina, Jacobsen, Ilse D., Schröder, Bernd

مصطلحات موضوعية: Antimicrobial responses, Fungal infection, Lysosomes, Pattern recognition receptors, Phagocytosis, Antimikrobielle Reaktionen, Pilzinfektion, Lysosomen, Mustererkennungsrezeptoren, Phagozytose, info:eu-repo/classification/ddc/500, ddc:500

الوصف: Sensing of pathogens by pattern recognition receptors (PRR) is critical to initiate protective host defence reactions. However, activation of the immune system has to be carefully titrated to avoid tissue damage necessitating mechanisms to control and terminate PRR signalling. Dectin-1 is a PRR for fungal β-glucans on immune cells that is rapidly internalised after ligand-binding. Here, we demonstrate that pathogen recognition by the Dectin-1a isoform results in the formation of a stable receptor fragment devoid of the ligand binding domain. This fragment persists in phagosomal membranes and contributes to signal transduction which is terminated by the intramembrane proteases Signal Peptide Peptidase-like (SPPL) 2a and 2b. Consequently, immune cells lacking SPPL2b demonstrate increased anti-fungal ROS production, killing capacity and cytokine responses. The identified mechanism allows to uncouple the PRR signalling response from delivery of the pathogen to degradative compartments and identifies intramembrane proteases as part of a regulatory circuit to control anti-fungal immune responses.

العلاقة: 1880; info:eu-repo/grantAgreement/Deutsche Forschungsgemeinschaft/SFB 877: Proteolyse als regulatorisches Ereignis in der Pathophysiologie/125440785//Charakterisierung der in vivo Funktionen der Signal-peptide-peptidase-like 2 Intramembranproteasen/B07; info:eu-repo/grantAgreement/Deutsche Forschungsgemeinschaft/FOR 2290: Intramembrane Proteolyse Verstehen/263531414/

الإتاحة: https://tud.qucosa.de/id/qucosa%3A91419Test
https://tud.qucosa.de/api/qucosa%3A91419/attachment/ATT-0Test/

المؤلفون: Tunger, Antje, Sommer, Ulrich, Wehner, Rebekka, Kubasch, Anne Sophie, Grimm, Marc-Oliver, Bachmann, Michael Philipp, Platzbecker, Uwe, Bornhäuser, Martin, Baretton, Gustavo, Schmitz, Marc

مصطلحات موضوعية: cancer immunotherapy, immune monitoring, immune checkpoints, programmed cell death protein 1, programmed cell death 1 ligand 1, info:eu-repo/classification/ddc/610, ddc:610

الوصف: The administration of antibodies blocking the immune checkpoint molecules programmed cell death protein 1 (PD-1) or programmed cell death 1 ligand 1 (PD-L1) has evolved as a very promising treatment option for cancer patients. PD-1/PD-L1 inhibition has significantly enhanced expansion, cytokine secretion, and cytotoxic activity of CD4+ and CD8+ T lymphocytes, resulting in enhanced antitumor responses. Anti-PD-1 or anti-PD-L1 therapy has induced tumor regression and improved clinical outcome in patients with different tumor entities, including melanoma, non-small-cell lung cancer, and renal cell carcinoma. These findings led to the approval of various anti-PD-1 or anti-PD-L1 antibodies for the treatment of tumor patients. However, the majority of patients have failed to respond to this treatment modality. Comprehensive immune monitoring of clinical trials led to the identification of potential biomarkers distinguishing between responders and non-responders, the discovery of modes of treatment resistance, and the design of improved immunotherapeutic strategies. In this review article, we summarize the evolving landscape of biomarkers for anti-PD-1 or anti-PD-L1 therapy.

العلاقة: 1534

الإتاحة: https://ul.qucosa.de/id/qucosa%3A84639Test
https://ul.qucosa.de/api/qucosa%3A84639/attachment/ATT-0Test/

المؤلفون: Kubasch, Anne Sophie, Wehner, Rebekka, Bazzurri, Serena, Tunger, Antje, Stasik, Sebastian, Garzarolli, Marlene, Meinel, Jörn, Baretton, Gustavo, Meier, Friedegund, Thiede, Christian, Schmitz, Marc, Platzbecker, Uwe

مصطلحات موضوعية: Cancer cells, immune-checkpoint receptor programmed cell death protein, tumor microenvironment, Technische Universität Dresden, Publishing Fund, Krebszellen, Immun-Checkpoint-Rezeptor-programmiertes Zelltodprotein, Tumormikroumgebung, Technische Universität Dresden, Publikationsfond, info:eu-repo/classification/ddc/610, ddc:610

الوصف: Cancer cells use the interaction between immune-checkpoint receptor programmed cell death protein 1 (PD-1) on activated T cells and programmed cell death ligand 1 (PD-L1) on tumor cells and various cell types of the tumor microenvironment to evade immune surveillance. Blocking the interaction between PD-1 and PD-L1 with checkpoint inhibitors can improve T-cell reactions and mediate efficient antitumor activity in a variety of solid tumors including melanoma. However, clinical data from patients with myeloid diseases that are treated with these agents are limited to clinical trials in advanced disease. Pembrolizumab (PEM) is a humanized monoclonal antibody of the immunoglobulin G4/κ isotype designed to block PD-1/PD-L1 interactions and is approved for various solid tumors including advanced melanoma.

الإتاحة: https://tud.qucosa.de/id/qucosa%3A34908Test
https://tud.qucosa.de/api/qucosa%3A34908/attachment/ATT-0Test/

المؤلفون: Bachmann, Michael, Bartsch, Holger, Kurien, Biji T., Scofield, Robert Hal, Temme, Achim, Schäkel, Knut, Zhao, Senming, Rieber, E. Peter, Schmitz, Marc, Wehner, Rebekka, Schwarzer, Adrian, Cartellieri, Marc, Stamova, Slava, Bippes, Claudia C.

مرشدي الرسالة: PLOS

المصدر: PLoS One. Volume 6 (2011) Bd. 1, e16315, 10.1371/journal.pone.0016315, ISSN 1932-6203

مصطلحات موضوعية: T-Zellen, Antikörper, Zellbindung, Klonung, antigenpräsentierende Zellen, Diagramme, cytotoxische T-Zellen, Hauptgewebeverträglichkeitskomplex, T-cells, Antibodies, cell binding, cloning, antigen-presenting cells, graphs, cytotoxic t-cells, major histocompadibility complex, ddc:610, rvk:XA 10000

الوصف: Background Previously, we identified a major myeloid-derived proinflammatory subpopulation of human blood dendritic cells which we termed slanDCs (e.g. Schäkel et al. (2006) Immunity 24, 767–777). The slan epitope is an O-linked sugar modification (6-sulfo LacNAc, slan) of P-selectin glycoprotein ligand-1 (PSGL-1). As slanDCs can induce neoantigen-specific CD4+ T cells and tumor-reactive CD8+ cytotoxic T cells, they appear as promising targets for an in vivo delivery of antigens for vaccination. However, tools for delivery of antigens to slanDCs were not available until now. Moreover, it is unknown whether or not antigens delivered via the slan epitope can be taken up, properly processed and presented by slanDCs to T cells. Methodology/Principal Findings Single chain fragment variables were prepared from presently available decavalent monoclonal anti-slan IgM antibodies but failed to bind to slanDCs. Therefore, a novel multivalent anti-slanDC scaffold was developed which consists of two components: (i) a single chain bispecific recombinant diabody (scBsDb) that is directed on the one hand to the slan epitope and on the other hand to a novel peptide epitope tag, and (ii) modular (antigen-containing) linker peptides that are flanked at both their termini with at least one peptide epitope tag. Delivery of a Tetanus Toxin-derived antigen to slanDCs via such a scBsDb/antigen scaffold allowed us to recall autologous Tetanus-specific memory T cells. Conclusions/Significance In summary our data show that (i) the slan epitope can be used for delivery of antigens to this class of human-specific DCs, and (ii) antigens bound to the slan epitope can be taken up by slanDCs, processed and presented to T cells. Consequently, our novel modular scaffold system may be useful for the development of human vaccines.

وصف الملف: application/pdf

الإتاحة: http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-186316Test
http://www.qucosa.de/fileadmin/data/qucosa/documents/18631/journal.pone.0016315.pdfTest

المؤلفون: Platzbecker, Uwe, Ferrer, Ruben A., Wobus, Manja, List, Catrin, Wehner, Rebekka, Schönefeldt, Claudia, Brocard, Barbara, Mohr, Brigitte, Rauner, Martina, Schmitz, Marc, Stiehler, Maik, Ehninger, Gerhard, Hofbauer, Lorenz C., Bornhäuser, Martin

مرشدي الرسالة: Ferrata Storti Foundation

المصدر: Haematologica, Volume 98 (2013) Bd. 11, ISSN 1677–1685; doi:10.3324/haematol.2013.083972

مصطلحات موضوعية: Knochenmark, Zellen, Knochenmarkspender, Stromazellen, bone marrow, cells, stromal cells, ddc:610, rvk:XA 10000

الوصف: The contribution of the bone marrow microenvironment in myelodysplastic syndrome is controversial. We therefore analyzed the functional properties of primary mesenchymal stromal cells from patients with myelodysplastic syndrome in the presence or absence of lenalidomide. Compared to healthy controls, clonality and growth were reduced across all disease stages. Furthermore, differentiation defects and particular expression of adhesion and cell surface molecules (e.g. CD166, CD29, CD146) were detected. Interestingly, the levels of stromal derived factor 1-alpha in patients’ cells culture supernatants were almost 2-fold lower (P

وصف الملف: application/pdf

الإتاحة: http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-178822Test
http://www.qucosa.de/fileadmin/data/qucosa/documents/17882/1677.full.pdfTest

المؤلفون: Wehner, Rebekka, Dietze, Kristin, Bachmann, Michael, Schmitz, Marc

المصدر: J Innate Immun 2011;3:258–263, ISSN: 1662-811X

مصطلحات موضوعية: info:eu-repo/classification/ddc/610, ddc:610, angeborene Immunität, natürliche Killerzellen, NK-Zellen, dendritische Zellen, Dendritic cells, Natural killer cells, Innate immunity

الوصف: Dendritic cells (DCs) are professional antigen-presenting cells, which display an extraordinary capacity to induce T-cell responses. Recent findings revealed that DCs also play a crucial role in the activation of natural killer (NK) cells representing important effectors in the innate immune defense against viruses and tumors. Here, we summarize various studies investigating the bidirectional crosstalk between human DCs and NK cells. In this context, it has been reported that DCs efficiently enhance CD69 expression, proliferation, interferon (IFN)-γ secretion and cytotoxic activity of NK cells. Cell membrane-associated molecules as well as soluble factors such as interleukin-12, tumor necrosis factor-α and type I IFNs contributed to DC-mediated NK cell activation. Reciprocally, the ability of human NK cells to enhance the immunostimulatory capacity of DCs was shown. Thus, NK cells promoted the maturation of DCs and markedly augmented their capacity to produce proinflammatory cytokines and to stimulate T-cell responses. The NK cell-mediated effects on DCs were dependent on cell membrane-associated molecules such as NKp30 and soluble factors such as tumor necrosis factor-α and IFN-γ. In conclusion, the reciprocal activating interaction between human DCs and NK cells may play a pivotal role in the immune defense against viruses and tumors.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

الإتاحة: https://tud.qucosa.de/id/qucosa%3A27732Test
https://tud.qucosa.de/api/qucosa%3A27732/attachment/ATT-0Test/

المؤلفون: Platzbecker, Uwe, Ferrer, Ruben A., Wobus, Manja, List, Catrin, Wehner, Rebekka, Schönefeldt, Claudia, Brocard, Barbara, Mohr, Brigitte, Rauner, Martina, Schmitz, Marc, Stiehler, Maik, Ehninger, Gerhard, Hofbauer, Lorenz C., Bornhäuser, Martin

مصطلحات موضوعية: Knochenmark, Zellen, Knochenmarkspender, Stromazellen, bone marrow, cells, stromal cells, info:eu-repo/classification/ddc/610, ddc:610

الوصف: The contribution of the bone marrow microenvironment in myelodysplastic syndrome is controversial. We therefore analyzed the functional properties of primary mesenchymal stromal cells from patients with myelodysplastic syndrome in the presence or absence of lenalidomide. Compared to healthy controls, clonality and growth were reduced across all disease stages. Furthermore, differentiation defects and particular expression of adhesion and cell surface molecules (e.g. CD166, CD29, CD146) were detected. Interestingly, the levels of stromal derived factor 1-alpha in patients’ cells culture supernatants were almost 2-fold lower (P

الإتاحة: https://tud.qucosa.de/id/qucosa%3A28910Test
https://tud.qucosa.de/api/qucosa%3A28910/attachment/ATT-0Test/