@article{ZieglerWeissSchmittetal.2017,
  author    = {Ziegler, Sabrina and Weiss, Esther and Schmitt, Anna-Lena and Schlegel, Jan and Burgert, Anne and Terpitz, Ulrich and Sauer, Markus and Moretta, Lorenzo and Sivori, Simona and Leonhardt, Ines and Kurzai, Oliver and Einsele, Hermann and Loeffler, Juergen},
  title     = {CD56 Is a Pathogen Recognition Receptor on Human Natural Killer Cells},
  series = {Scientific Reports},
  volume    = {7},
  journal   = {Scientific Reports},
  number    = {6138},
  doi       = {10.1038/s41598-017-06238-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170637},
  year      = {2017},
  abstract  = {Aspergillus (A.) fumigatus is an opportunistic fungal mold inducing invasive aspergillosis (IA) in immunocompromised patients. Although antifungal activity of human natural killer (NK) cells was shown in previous studies, the underlying cellular mechanisms and pathogen recognition receptors (PRRs) are still unknown. Using flow cytometry we were able to show that the fluorescence positivity of the surface receptor CD56 significantly decreased upon fungal contact. To visualize the interaction site of NK cells and A. fumigatus we used SEM, CLSM and dSTORM techniques, which clearly demonstrated that NK cells directly interact with A. fumigatus via CD56 and that CD56 is re-organized and accumulated at this interaction site time-dependently. The inhibition of the cytoskeleton showed that the receptor re-organization was an active process dependent on actin re-arrangements. Furthermore, we could show that CD56 plays a role in the fungus mediated NK cell activation, since blocking of CD56 surface receptor reduced fungal mediated NK cell activation and reduced cytokine secretion. These results confirmed the direct interaction of NK cells and A. fumigatus, leading to the conclusion that CD56 is a pathogen recognition receptor. These findings give new insights into the functional role of CD56 in the pathogen recognition during the innate immune response.},
  language  = {en}
}
@article{NeuchelFuerstNiederwieseretal.2017,
  author    = {Neuchel, Christine and F{\"u}rst, Daniel and Niederwieser, Dietger and Bunjes, Donald and Tsamadou, Chrysanthi and Wulf, Gerald and Pfreundschuh, Michael and Wagner, Eva and Stuhler, Gernot and Einsele, Hermann and Schrezenmeier, Hubert and Mytilineos, Joannis},
  title     = {Impact of donor activating KIR genes on HSCT outcome in C1-ligand negative myeloid disease patients transplanted with unrelated donors - a retrospective study},
  series = {PLOS One},
  volume    = {12},
  journal   = {PLOS One},
  number    = {1},
  doi       = {10.1371/journal.pone.0169512},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180995},
  pages     = {39},
  year      = {2017},
  abstract  = {Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome. Our study, based on a cohort of 200 C1-negative patients, confirmed these findings for the endpoints: overall survival (OS: HR = 1.41, CI = 1.14-1.74, p = 0.0012), disease free survival (DFS: HR = 1.27, CI = 1.05-1.53, p = 0.015), treatment related mortality (TRM: HR = 1.41, CI = 1.01-1.96, p = 0.04), and relapse incidence (RI: HR = 1.33, CI = 1.01-1.75, p = 0.04) all being inferior when compared to C1-positive patients (n = 1246). Subsequent analysis showed that these findings applied for patients with myeloid malignancies but not for patients with lymphoproliferative diseases (OS: myeloid: HR = 1.51, CI = 1.15-1.99, p = 0.003; lymphoblastic: HR = 1.26, CI = 0.91-1.75, p = 0.16; DFS: myeloid: HR = 1.31, CI = 1.01-1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90-1.61, p = 0.21; RI: myeloid: HR = 1.31, CI = 1.01-1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90-1.61, p = 0.21). Interestingly, within the C1-negative patient group, transplantation with KIR2DS2 resulted in better OS (9/10 matched: HR = 0.24, CI = 0.08-0.67, p = 0.007) as well as DFS (9/10 matched: HR = 0,26, CI = 0.11-0.60, p = 0.002), and transplantation with KIR2DS1 positive donors was associated with a decreased RI (HR = 0.30, CI = 0.13-0.69, p = 0.005). TRM was increased when the donor was positive for KIR2DS1 (HR = 2.61, CI = 1.26-5.41, p = 0.001). Our findings suggest that inclusion of KIR2DS1/2/5 and KIR3DS1-genotyping in the unrelated donor search algorithm of C1-ligand negative patients with myeloid malignancies may prove to be of clinical relevance.},
  language  = {en}
}
@article{LapaHerrmannSchirbeletal.2017,
  author    = {Lapa, Constantin and Herrmann, Ken and Schirbel, Andreas and H{\"a}nscheid, Heribert and L{\"u}ckerath, Katharina and Schottelius, Margret and Kircher, Malte and Werner, Rudolf A. and Schreder, Martin and Samnick, Samuel and Kropf, Saskia and Knop, Stefan and Buck, Andreas K. and Einsele, Hermann and Wester, Hans-Juergen and Kort{\"u}m, K. Martin},
  title     = {CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed multiple myeloma},
  series = {Theranostics},
  volume    = {7},
  journal   = {Theranostics},
  number    = {6},
  doi       = {10.7150/thno.19050},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172095},
  pages     = {1589-1597},
  year      = {2017},
  abstract  = {C-X-C-motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. We have recently reported promising first-in-man experience with CXCR4-directed endoradiotherapy (ERT) in multiple myeloma (MM). Eight heavily pretreated MM patients underwent a total of 10 ERT cycles (7 patients with 1 cycle and a single patient with 3 cycles). ERT was administered in combination with chemotherapy and autologous stem cell support. End points were occurrence and timing of adverse events, progression-free and overall survival. ERT was overall well tolerated without any unexpected acute adverse events or changes in vital signs. With absorbed tumor doses >30-70 Gy in intra- or extramedullary lesions, significant anti-myeloma activity was observed with 1 patient achieving complete remission and 5/8 partial remission. Directly after ERT major infectious complications were seen in one patient who died from sepsis 22 days after ERT, another patient with high tumor burden experienced lethal tumor lysis syndrome. Median progression-free survival was 54 days (range, 13-175), median overall survival was 223 days (range, 13-313). During follow-up (6 patients available), one patient died from infectious complications, 2/8 from disease progression, the remaining 3/8 patients are still alive. CXCR4-directed ERT was well-tolerated and exerted anti-myeloma activity even at very advanced stage MM with presence of extramedullary disease. Further assessment of this novel treatment option is highly warranted.},
  language  = {en}
}
@article{TsamadouFuerstVucinicetal.2017,
  author    = {Tsamadou, Chrysanthi and F{\"u}rst, Daniel and Vucinic, Vladan and Bunjes, Donald and Neuchel, Christine and Mytilineos, Daphne and Gramatzki, Martin and Arnold, Renate and Wagner, Eva Maria and Einsele, Hermann and M{\"u}ller, Carlheinz and Schrezenmeier, Hubert and Mytilineos, Joannis},
  title     = {Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients},
  series = {Haematologica},
  volume    = {102},
  journal   = {Haematologica},
  number    = {11},
  doi       = {10.3324/haematol.2017.169805},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173325},
  pages     = {1947-1955},
  year      = {2017},
  abstract  = {The immunomodulatory role of human leukocyte antigen (HLA)-E in hematopoietic stem cell transplantation (HSCT) has not been extensively investigated. To this end, we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E, in order to study the effect of HLA-E as a natural killer (NK)-alloreactivity mediator on HSCT outcome in an acute leukemia (AL) setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both univariate (53\% vs. 38\%, P=0.002, 5-year OS) and multivariate (hazard ratio (HR)=0.63, confidence interval (CI) 95\%=0.48-0.83, P=0.001) analyses. Further subgroup analysis demonstrated that the positive effect of HLA-E mismatch was significant and pronounced in advanced disease patients (n=120) (5-year OS: 50\% vs. 18\%, P=0.005; HR=0.40, CI 95\%=0.22-0.72, P=0.002; results from univariate and multivariate analyses, respectively). The study herein is the first to report an association between HLA-E incompatibility and improved post-transplant prognosis in AL patients who have undergone matched unrelated HSCT. Combined NK and T cell HLA-E-mediated mechanisms may account for the better outcomes observed. Notwithstanding the necessity for in vitro and confirmational studies, our findings highlight the clinical relevance of HLA-E matching and strongly support prospective HLA-E screening upon donor selection for matched AL unrelated HSCTs.},
  language  = {en}
}
@article{HellmannLotherWursteretal.2017,
  author    = {Hellmann, Anna-Maria and Lother, Jasmin and Wurster, Sebastian and Lutz, Manfred B. and Schmitt, Anna Lena and Morton, Charles Oliver and Eyrich, Matthias and Czakai, Kristin and Einsele, Hermann and Loeffler, Juergen},
  title     = {Human and Murine Innate Immune Cell Populations Display Common and Distinct Response Patterns during Their In Vitro Interaction with the Pathogenic Mold Aspergillus fumigatus},
  series = {Frontiers in Immunology},
  volume    = {8},
  journal   = {Frontiers in Immunology},
  number    = {1716},
  doi       = {10.3389/fimmu.2017.01716},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169926},
  year      = {2017},
  abstract  = {Aspergillus fumigatus is the main cause of invasive fungal infections occurring almost exclusively in immunocompromised patients. An improved understanding of the initial innate immune response is key to the development of better diagnostic tools and new treatment options. Mice are commonly used to study immune defense mechanisms during the infection of the mammalian host with A. fumigatus. However, little is known about functional differences between the human and murine immune response against this fungal pathogen. Thus, we performed a comparative functional analysis of human and murine dendritic cells (DCs), macrophages, and polymorphonuclear cells (PMNs) using standardized and reproducible working conditions, laboratory protocols, and readout assays. A. fumigatus did not provoke identical responses in murine and human immune cells but rather initiated relatively specific responses. While human DCs showed a significantly stronger upregulation of their maturation markers and major histocompatibility complex molecules and phagocytosed A. fumigatus more efficiently compared to their murine counterparts, murine PMNs and macrophages exhibited a significantly stronger release of reactive oxygen species after exposure to A. fumigatus. For all studied cell types, human and murine samples differed in their cytokine response to conidia or germ tubes of A. fumigatus. Furthermore, Dectin-1 showed inverse expression patterns on human and murine DCs after fungal stimulation. These specific differences should be carefully considered and highlight potential limitations in the transferability of murine host-pathogen interaction studies.},
  language  = {en}
}
@article{LapaGarciaVellosoLueckerathetal.2017,
  author    = {Lapa, Constantin and Garcia-Velloso, Maria J. and L{\"u}ckerath, Katharina and Samnick, Samuel and Schreder, Martin and Otero, Paula Rodriguez and Schmid, Jan-Stefan and Herrmann, Ken and Knop, Stefan and Buck, Andreas K. and Einsele, Hermann and San-Miguel, Jesus and Kort{\"u}m, Klaus Martin},
  title     = {\(^{11}\)C-methionine-PET in multiple myeloma: a combined study from two different institutions},
  series = {Theranostics},
  volume    = {7},
  journal   = {Theranostics},
  number    = {11},
  doi       = {10.7150/thno.20491},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172038},
  pages     = {2956-2964},
  year      = {2017},
  abstract  = {\(^{11}\)C-methionine (MET) has recently emerged as an accurate marker of tumor burden and disease activity in patients with multiple myeloma (MM). This dual-center study aimed at further corroboration of the superiority of MET as positron emission tomography (PET) tracer for staging and re-staging MM, as compared to \(^{18}\)F-2`-deoxy-2`-fluoro-D-glucose (FDG). 78 patients with a history of solitary plasmacytoma (n=4), smoldering MM (SMM, n=5), and symptomatic MM (n=69) underwent both MET- and FDG-PET/computed tomography (CT) at the University Centers of W{\"u}rzburg, Germany and Navarra, Spain. Scans were compared on a patient and on a lesion basis. Inter-reader agreement was also evaluated. In 2 patients, tumor biopsies for verification of discordant imaging results were available. MET-PET detected focal lesions (FL) in 59/78 subjects (75.6\%), whereas FDG-PET/CT showed lesions in only 47 patients (60.3\%; p<0.01), accordingly disease activity would have been missed in 12 patients. Directed biopsies of discordant results confirmed MET-PET/CT results in both cases. MET depicted more FL in 44 patients (56.4\%; p<0.01), whereas in two patients (2/78), FDG proved superior. In the remainder (41.0\%, 32/78), both tracers yielded comparable results. Inter-reader agreement for MET was higher than for FDG (κ = 0.82 vs κ = 0.72). This study demonstrates higher sensitivity of MET in comparison to standard FDG to detect intra- and extramedullary MM including histologic evidence of FDG-negative, viable disease exclusively detectable by MET-PET/CT. MET holds the potential to replace FDG as functional imaging standard for staging and re-staging of MM.},
  language  = {en}
}