@article{EyrichRachorSchreiberetal.2013,
  author    = {Eyrich, Matthias and Rachor, Johannes and Schreiber, Susanne C. and W{\"o}lfl, Matthias and Schlegel, Paul G.},
  title     = {Dendritic cell vaccination in pediatric gliomas: lessons learnt and future perspectives},
  series = {Frontiers in Pediatrics},
  journal   = {Frontiers in Pediatrics},
  doi       = {10.3389/fped.2013.00012},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96937},
  year      = {2013},
  abstract  = {Immunotherapy of malignant gliomas with autologous dendritic cells (DCs) in addition to surgery and radiochemotherapy has been a focus of intense research during the past decade. Since both children and adults are affected by this highly aggressive brain tumor, 10-15\% of the several hundred vaccinated patients represent children, making pediatric glioma patients the largest uniform pediatric vaccination cohort so far. In general, DC vaccination in malignant gliomas has been shown to be safe and several studies with a non-vaccinated control group could clearly demonstrate a survival benefit for the vaccinated patients. Interestingly, children and adolescents below 21 years of age seem to benefit even more than adult patients. This review summarizes the findings of the 25 clinical trials published so far and gives a perspective how DC vaccination could be implemented as part of multimodal therapeutic strategies in the near future.},
  language  = {en}
}
@article{DietlSchwinnDietletal.2016,
  author    = {Dietl, Sebastian and Schwinn, Stefanie and Dietl, Susanne and Riedl, Simone and Deinlein, Frank and Rutkowski, Stefan and von Bueren, Andre O. and Krauss, J{\"u}rgen and Schweitzer, Tilmann and Vince, Giles H. and Picard, Daniel and Eyrich, Matthias and Rosenwald, Andreas and Ramaswamy, Vijay and Taylor, Michael D. and Remke, Marc and Monoranu, Camelia M. and Beilhack, Andreas and Schlegel, Paul G. and W{\"o}lfl, Matthias},
  title     = {MB3W1 is an orthotopic xenograft model for anaplastic medulloblastoma displaying cancer stem cell- and Group 3-properties},
  series = {BMC Cancer},
  volume    = {16},
  journal   = {BMC Cancer},
  number    = {115},
  doi       = {10.1186/s12885-016-2170-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145877},
  year      = {2016},
  abstract  = {Background Medulloblastoma is the most common malignant brain tumor in children and can be divided in different molecular subgroups. Patients whose tumor is classified as a Group 3 tumor have a dismal prognosis. However only very few tumor models are available for this subgroup. Methods We established a robust orthotopic xenograft model with a cell line derived from the malignant pleural effusions of a child suffering from a Group 3 medulloblastoma. Results Besides classical characteristics of this tumor subgroup, the cells display cancer stem cell characteristics including neurosphere formation, multilineage differentiation, CD133/CD15 expression, high ALDH-activity and high tumorigenicity in immunocompromised mice with xenografts exactly recapitulating the original tumor architecture. Conclusions This model using unmanipulated, human medulloblastoma cells will enable translational research, specifically focused on Group 3 medulloblastoma.},
  language  = {en}
}
@article{KredelKunzmannSchlegeletal.2017,
  author    = {Kredel, Markus and Kunzmann, Steffen and Schlegel, Paul-Gerhardt and W{\"o}lfl, Matthias and Nordbeck, Peter and B{\"u}hler, Christoph and Lotz, Christopher and Lepper, Philipp M. and Wirbelauer, Johannes and Roewer, Norbert and Muellenbach, Ralf M.},
  title     = {Double Peripheral Venous and Arterial Cannulation for Extracorporeal Membrane Oxygenation in Combined Septic and Cardiogenic Shock},
  series = {American Journal of Case Reports},
  volume    = {18},
  journal   = {American Journal of Case Reports},
  doi       = {10.12659/AJCR.902485},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158193},
  pages     = {723-727},
  year      = {2017},
  abstract  = {Background: The use of venoarterial extracorporeal membrane oxygenation (va-ECMO) via peripheral cannulation for septic shock is limited by blood flow and increased afterload for the left ventricle. Case Report: A 15-year-old girl with acute myelogenous leukemia, suffering from severe septic and cardiogenic shock, was treated by venoarterial extracorporeal membrane oxygenation (va-ECMO). Sufficient extracorporeal blood flow matching the required oxygen demand could only be achieved by peripheral cannulation of both femoral arteries. Venous drainage was performed with a bicaval cannula inserted via the left V. femoralis. To accomplish left ventricular unloading, an additional drainage cannula was placed in the left atrium via percutaneous atrioseptostomy (va-va-ECMO). Cardiac function recovered and the girl was weaned from the ECMO on day 6. Successful allogenic stem cell transplantation took place 2 months later. Conclusions: In patients with vasoplegic septic shock and impaired cardiac contractility, double peripheral venoarterial extracorporeal membrane oxygenation (va-va-ECMO) with transseptal left atrial venting can by a lifesaving option.},
  language  = {en}
}
@article{KrakowCrescimoneBartelsetal.2019,
  author    = {Krakow, S{\"o}ren and Crescimone, Marie L. and Bartels, Charlotte and Wiegering, Verena and Eyrich, Matthias and Schlegel, Paul G. and W{\"o}lfl, Matthias},
  title     = {Re-expression of CD14 in response to a combined IL-10/TLR stimulus defines monocyte-derived cells with an immunoregulatory phenotype},
  series = {Frontiers in Immunology},
  volume    = {10},
  journal   = {Frontiers in Immunology},
  number    = {1484},
  doi       = {10.3389/fimmu.2019.01484},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201537},
  year      = {2019},
  abstract  = {Interleukin 10 is a central regulator of the antigen-presenting function of myeloid cells. It exerts immunomodulatory effects in vivo and induces a regulatory phenotype in monocyte-derived cells in vitro. We analyzed phenotype and function of monocytic cells in vitro in relation to the cytokine milieu and the timing of TLR-based activation. In GM-CSF/IL-4 cultured human monocytic cells, we identified two, mutually exclusive cell populations arising from undifferentiated cells: CD83\(^+\) fully activated dendritic cells and CD14\(^+\) macrophage like cells. Re-expression of CD14 occurs primarily after a sequential trigger with a TLR signal following IL-10 preincubation. This cell population with re-expressed CD14 greatly differs in phenotype and function from the CD83+ cells. Detailed analysis of individual subpopulations reveals that exogenous IL-10 is critical for inducing the shift toward the CD14\(^+\) population, but does not affect individual changes in marker expression or cell function in most cases. Thus, plasticity of CD14 expression, defining a subset of immunoregulatory cells, is highly relevant for the composition of cellular products (such as DC vaccines) as it affects the function of the total product.},
  language  = {en}
}
@article{GierlichLexTechnauetal.2020,
  author    = {Gierlich, Philipp and Lex, Veronika and Technau, Antje and Keupp, Anne and Morper, Lorenz and Glunz, Amelie and Sennholz, Hanno and Rachor, Johannes and Sauer, Sascha and Marcu, Ana and Grigoleit, G{\"o}tz Ulrich and W{\"o}lfl, Matthias and Schlegel, Paul G. and Eyrich, Matthias},
  title     = {Prostaglandin E\(_2\) in a TLR3‑ and 7/8‑agonist‑based DC maturation cocktail generates mature, cytokine‑producing, migratory DCs but impairs antigen cross‑presentation to CD8\(^+\) T cells},
  series = {Cancer Immunology, Immunotherapy},
  volume    = {69},
  journal   = {Cancer Immunology, Immunotherapy},
  issn      = {0340-7004},
  doi       = {10.1007/s00262-019-02470-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232311},
  pages     = {1029-1042},
  year      = {2020},
  abstract  = {Mature dendritic cells (DCs) represent cellular adjuvants for optimal antigen presentation in cancer vaccines. Recently, a combination of prostaglandin E\(_2\) (PGE\(_2\)) with Toll-like receptor agonists (TLR-P) was proposed as a new standard to generate superior cytokine-producing DCs with high migratory capacity. Here, we compare TLR-P DCs with conventional DCs matured only with the proinflammatory cytokines TNFα and IL-1ß (CDCs), focussing on the interaction of resulting DCs with CD8\(^+\) T-cells. TLR-P matured DCs showed elevated expression of activation markers such as CD80 and CD83 compared to CDCs, together with a significantly higher migration capacity. Secretion of IL-6, IL-8, IL-10, and IL-12 was highest after 16 h in TLR-P DCs, and only TLR-P DCs secreted active IL-12p70. TLR-P DCs as well as CDCs successfully primed multifunctional CD8\(^+\) T-cells from na{\"i}ve precursors specific for the peptide antigens Melan-A, NLGN4X, and PTP with comparable priming efficacy and T-cell receptor avidity. CD8\(^+\) T-cells primed by TLR-P DCs showed significantly elevated expression of the integrin VLA-4 and a trend for higher T-cell numbers after expansion. In contrast, TLR-P DCs displayed a substantially reduced capability to cross-present CMVpp65 protein antigen to pp65-specific T cells, an effect that was dose-dependent on PGE2 during DC maturation and reproducible with several responder T-cell lines. In conclu-sion, TLR-P matured DCs might be optimal presenters of antigens not requiring processing such as short peptides. However, PGE\(_2\) seems less favorable for maturation of DCs intended to process and cross-present more complex vaccine antigens such as lysates, proteins or long peptides.},
  language  = {en}
}
@article{SchwinnMokhtariThuseketal.2021,
  author    = {Schwinn, Stefanie and Mokhtari, Zeinab and Thusek, Sina and Schneider, Theresa and Sir{\´e}n, Anna-Leena and Tiemeyer, Nicola and Caruana, Ignazio and Miele, Evelina and Schlegel, Paul G. and Beilhack, Andreas and W{\"o}lfl, Matthias},
  title     = {Cytotoxic effects and tolerability of gemcitabine and axitinib in a xenograft model for c-myc amplified medulloblastoma},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-021-93586-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261476},
  year      = {2021},
  abstract  = {Medulloblastoma is the most common high-grade brain tumor in childhood. Medulloblastomas with c-myc amplification, classified as group 3, are the most aggressive among the four disease subtypes resulting in a 5-year overall survival of just above 50\%. Despite current intensive therapy regimens, patients suffering from group 3 medulloblastoma urgently require new therapeutic options. Using a recently established c-myc amplified human medulloblastoma cell line, we performed an in-vitro-drug screen with single and combinatorial drugs that are either already clinically approved or agents in the advanced stage of clinical development. Candidate drugs were identified in vitro and then evaluated in vivo. Tumor growth was closely monitored by BLI. Vessel development was assessed by 3D light-sheet-fluorescence-microscopy. We identified the combination of gemcitabine and axitinib to be highly cytotoxic, requiring only low picomolar concentrations when used in combination. In the orthotopic model, gemcitabine and axitinib showed efficacy in terms of tumor control and survival. In both models, gemcitabine and axitinib were better tolerated than the standard regimen comprising of cisplatin and etoposide phosphate. 3D light-sheet-fluorescence-microscopy of intact tumors revealed thinning and rarefication of tumor vessels, providing one explanation for reduced tumor growth. Thus, the combination of the two drugs gemcitabine and axitinib has favorable effects on preventing tumor progression in an orthotopic group 3 medulloblastoma xenograft model while exhibiting a favorable toxicity profile. The combination merits further exploration as a new approach to treat high-risk group 3 medulloblastoma.},
  language  = {en}
}
@article{BaeuerleinQureischiMokhtarietal.2021,
  author    = {B{\"a}uerlein, Carina A. and Qureischi, Musga and Mokhtari, Zeinab and Tabares, Paula and Brede, Christian and Jord{\´a}n Garrote, Ana-Laura and Riedel, Simone S. and Chopra, Martin and Reu, Simone and Mottok, Anja and Arellano-Viera, Estibaliz and Graf, Carolin and Kurzwart, Miriam and Schmiedgen, Katharina and Einsele, Hermann and W{\"o}lfl, Matthias and Schlegel, Paul-Gerhardt and Beilhack, Andreas},
  title     = {A T-Cell Surface Marker Panel Predicts Murine Acute Graft-Versus-Host Disease},
  series = {Frontiers in Immunology},
  volume    = {11},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2020.593321},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224290},
  year      = {2021},
  abstract  = {Acute graft-versus-host disease (aGvHD) is a severe and often life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). AGvHD is mediated by alloreactive donor T-cells targeting predominantly the gastrointestinal tract, liver, and skin. Recent work in mice and patients undergoing allo-HCT showed that alloreactive T-cells can be identified by the expression of α4β7 integrin on T-cells even before manifestation of an aGvHD. Here, we investigated whether the detection of a combination of the expression of T-cell surface markers on peripheral blood (PB) CD8\(^+\) T-cells would improve the ability to predict aGvHD. To this end, we employed two independent preclinical models of minor histocompatibility antigen mismatched allo-HCT following myeloablative conditioning. Expression profiles of integrins, selectins, chemokine receptors, and activation markers of PB donor T-cells were measured with multiparameter flow cytometry at multiple time points before the onset of clinical aGvHD symptoms. In both allo-HCT models, we demonstrated a significant upregulation of α4β7 integrin, CD162E, CD162P, and conversely, a downregulation of CD62L on donor T-cells, which could be correlated with the development of aGvHD. Other surface markers, such as CD25, CD69, and CC-chemokine receptors were not found to be predictive markers. Based on these preclinical data from mouse models, we propose a surface marker panel on peripheral blood T-cells after allo-HCT combining α4β7 integrin with CD62L, CD162E, and CD162P (cutaneous lymphocyte antigens, CLA, in humans) to identify patients at risk for developing aGvHD early after allo-HCT.},
  language  = {en}
}