TY  - JOUR
A1  - Klein-Hessling, Stefan
A1  - Muhammad, Khalid
A1  - Klein, Matthias
A1  - Pusch, Tobias
A1  - Rudolf, Ronald
A1  - Flöter, Jessica
A1  - Qureischi, Musga
A1  - Beilhack, Andreas
A1  - Vaeth, Martin
A1  - Kummerow, Carsten
A1  - Backes, Christian
A1  - Schoppmeyer, Rouven
A1  - Hahn, Ulrike
A1  - Hoth, Markus
A1  - Bopp, Tobias
A1  - Berberich-Siebelt, Friederike
A1  - Patra, Amiya
A1  - Avots, Andris
A1  - Müller, Nora
A1  - Schulze, Almut
A1  - Serfling, Edgar
T1  - NFATc1 controls the cytotoxicity of CD8\(^{+}\) T cells
JF  - Nature Communications
N2  - Cytotoxic T lymphocytes are effector CD8\(^{+}\) T cells that eradicate infected and malignant cells. Here we show that the transcription factor NFATc1 controls the cytotoxicity of mouse cytotoxic T lymphocytes. Activation of Nfatc1\(^{-/-}\) cytotoxic T lymphocytes showed a defective cytoskeleton organization and recruitment of cytosolic organelles to immunological synapses. These cells have reduced cytotoxicity against tumor cells, and mice with NFATc1-deficient T cells are defective in controlling Listeria infection. Transcriptome analysis shows diminished RNA levels of numerous genes in Nfatc1\(^{-/-}\) CD8\(^{+}\) T cells, including Tbx21, Gzmb and genes encoding cytokines and chemokines, and genes controlling glycolysis. Nfatc1\(^{-/-}\), but not Nfatc2\(^{-/-}\) CD8\(^{+}\) T cells have an impaired metabolic switch to glycolysis, which can be restored by IL-2. Genome-wide ChIP-seq shows that NFATc1 binds many genes that control cytotoxic T lymphocyte activity. Together these data indicate that NFATc1 is an important regulator of cytotoxic T lymphocyte effector functions.
KW  - cytotoxic T cells
KW  - lymphocyte activation
KW  - signal transduction
KW  - gene regulation
KW  - immune cells
KW  - NFATc1
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170353
VL  - 8
IS  - 511
ER  - 
TY  - JOUR
A1  - Metzenmacher, Martin
A1  - Váraljai, Renáta
A1  - Hegedüs, Balazs
A1  - Cima, Igor
A1  - Forster, Jan
A1  - Schramm, Alexander
A1  - Scheffler, Björn
A1  - Horn, Peter A.
A1  - Klein, Christoph A.
A1  - Szarvas, Tibor
A1  - Reis, Hennig
A1  - Bielefeld, Nicola
A1  - Roesch, Alexander
A1  - Aigner, Clemens
A1  - Kunzmann, Volker
A1  - Wiesweg, Marcel
A1  - Siveke, Jens T.
A1  - Schuler, Martin
A1  - Lueong, Smiths S.
T1  - Plasma Next Generation Sequencing and Droplet Digital-qPCR-Based Quantification of Circulating Cell-Free RNA for Noninvasive Early Detection of Cancer
JF  - Cancers
N2  - Early detection of cancer holds high promise for reducing cancer-related mortality. Detection of circulating tumor-specific nucleic acids holds promise, but sensitivity and specificity issues remain with current technology. We studied cell-free RNA (cfRNA) in patients with non-small cell lung cancer (NSCLC; n = 56 stage IV, n = 39 stages I-III), pancreatic cancer (PDAC, n = 20 stage III), malignant melanoma (MM, n = 12 stage III-IV), urothelial bladder cancer (UBC, n = 22 stage II and IV), and 65 healthy controls by means of next generation sequencing (NGS) and real-time droplet digital PCR (RT-ddPCR). We identified 192 overlapping upregulated transcripts in NSCLC and PDAC by NGS, more than 90% of which were noncoding. Previously reported transcripts (e.g., HOTAIRM1) were identified. Plasma cfRNA transcript levels of POU6F2-AS2 discriminated NSCLC from healthy donors (AUC = 0.82 and 0.76 for stages IV and I–III, respectively) and significantly associated (p = 0.017) with the established tumor marker Cyfra 21-1. cfRNA yield and POU6F2-AS transcript abundance discriminated PDAC patients from healthy donors (AUC = 1.0). POU6F2-AS2 transcript was significantly higher in MM (p = 0.044). In summary, our findings support further validation of cfRNA detection by RT-ddPCR as a biomarker for early detection of solid cancers.
KW  - liquid biopsy
KW  - cfRNA
KW  - cancer
KW  - ddPCR
KW  - NGS
KW  - POU6F2-AS2
KW  - early detection
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200553
SN  - 2072-6694
VL  - 12
IS  - 2
ER  - 
TY  - JOUR
A1  - Wagner-Drouet, Eva
A1  - Teschner, Daniel
A1  - Wolschke, Christine
A1  - Schäfer-Eckart, Kerstin
A1  - Gärtner, Johannes
A1  - Mielke, Stephan
A1  - Schreder, Martin
A1  - Kobbe, Guido
A1  - Hilgendorf, Inken
A1  - Klein, Stefan
A1  - Verbeek, Mareike
A1  - Ditschkowski, Markus
A1  - Koch, Martina
A1  - Lindemann, Monika
A1  - Schmidt, Traudel
A1  - Rascle, Anne
A1  - Barabas, Sascha
A1  - Deml, Ludwig
A1  - Wagner, Ralf
A1  - Wolff, Daniel
T1  - Comparison of cytomegalovirus-specific immune cell response to proteins versus peptides using an IFN-γ ELISpot assay after hematopoietic stem cell transplantation
JF  - Diagnostics
N2  - Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). Measuring CMV-specific cellular immunity may improve the risk stratification and management of patients. IFN-γ ELISpot assays, based on the stimulation of peripheral blood mononuclear cells with CMV pp65 and IE-1 proteins or peptides, have been validated in clinical settings. However, it remains unclear to which extend the T-cell response to synthetic peptides reflect that mediated by full-length proteins processed by antigen-presenting cells. We compared the stimulating ability of pp65 and IE-1 proteins and corresponding overlapping peptides in 16 HSCT recipients using a standardized IFN-γ ELISpot assay. Paired qualitative test results showed an overall 74.4% concordance. Discordant results were mainly due to low-response tests, with one exception. One patient with early CMV reactivation and graft-versus-host disease, sustained CMV DNAemia and high CD8\(^+\) counts showed successive negative protein-based ELISpot results but a high and sustained response to IE-1 peptides. Our results suggest that the response to exogenous proteins, which involves their uptake and processing by antigen-presenting cells, more closely reflects the physiological response to CMV infection, while the response to exogenous peptides may lead to artificial in vitro T-cell responses, especially in strongly immunosuppressed patients.
KW  - CMV
KW  - CMV-specific cellular immunity
KW  - hematopoietic stem cell transplantation
KW  - recall antigen
KW  - peptide
KW  - immune monitoring
KW  - IFN-γ ELISpot
KW  - T cells
KW  - antigen processing and presentation
KW  - immunosuppression
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228843
SN  - 2075-4418
VL  - 11
IS  - 2
ER  -