A5031776977- Glioma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Cancer Mechanisms and Therapy
- T-cell and B-cell Immunology
- Brain Metastases and Treatment
- Neuroblastoma Research and Treatments
- Chromatin Remodeling and Cancer
- Immune cells in cancer
- PARP inhibition in cancer therapy
- Sphingolipid Metabolism and Signaling
- Mechanisms of cancer metastasis
- ATP Synthase and ATPases Research
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Asthma and respiratory diseases
- Food Allergy and Anaphylaxis Research
- Pediatric health and respiratory diseases
- Radiopharmaceutical Chemistry and Applications
- Chemokine receptors and signaling
- Histone Deacetylase Inhibitors Research
- NF-κB Signaling Pathways
- Lung Cancer Research Studies
Leibniz Association
2022
Leibniz Institute for Immunotherapy
2022
University Hospital Regensburg
2018-2021
National Center for Tumor Diseases
2017-2019
Heidelberg University
2015-2019
German Cancer Research Center
2015-2019
University of Regensburg
2017
Institute of Immunology
2011
Medizinische Hochschule Hannover
2010
Rationale: Myeloid-derived suppressor cell (MDSC) expansion has been found to play a role in disease progression patients with cancer. However, the characteristics of MDSCs lung cancer are poorly understood.Objectives: We prospectively investigated and inflammatory factors tumor peripheral blood samples from resectable non–small studied their correlations prognosis.Methods: A complex analysis MDSC subsets mediators was performed using flow cytometry Bio-Plex assay.Measurements Main Results:...
Dendritic cells (DCs) represent the most potent inducers of adaptive immune responses. Depending on their activation phenotype, DCs drive naive T into distinct differentiation pathways. To achieve this, are present in virtually all tissues where they sample Ag and migrate to cell areas lymph nodes (LNs) spleen. Ample evidence exists demonstrating that sphingosine 1-phosphate (S1P) is an important modulator these processes, exerting its effects by binding S1P receptor S1P(1) and/or S1P(3)....
Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a surface receptor, is expressed on normal epithelial tissue and highly in cancers of high unmet medical need, such as non-small lung, pancreatic, colorectal cancer. CEACAM receptors undergo homo- heterophilic interactions thereby regulating homeostasis angiogenesis, cancer, tumor invasion metastasis. CEACAM6 expression malignant plasma cells inhibits antitumor activity T cells, we hypothesize similar function cancer cells....
Abstract Purpose: Successful immunotherapies for IDHmut gliomas require better knowledge of T-cell target antigens. Here, we elucidated their antigen repertoire recognized by spontaneous responses using an unbiased proteomic approach. Experimental Design: Protein fractionations tissue lysates from (n = 4) were performed. Fractions tested IFNγ ELISpot assay recognition through patients' T cells. Proteins immunogenic fractions identified mass spectrometry and validated in silico-predicted...
Endogenous antitumor effector T-cell responses and immune-suppressive regulatory T cells (Treg) critically influence the prognosis of patients with cancer, yet many mechanisms how this occurs remain unresolved. On basis an analysis function, antigen specificity, distribution tumor antigen-reactive Tregs in breast cancer transgenic mouse models, we showed that tumor-specific were selectively activated bone marrow (BM) egressed into peripheral blood. The BM was constantly depleted instead a...
The success of cancer immunotherapy is limited by resistance to immune checkpoint blockade. We therefore conducted a genetic screen identify genes that mediated against CTLs in anti-PD-L1 treatment-refractory human tumors. Using PD-L1-positive multiple myeloma cells cocultured with tumor-reactive bone marrow-infiltrating CTL as model, we identified calcium/calmodulin-dependent protein kinase 1D (CAMK1D) key modulator tumor-intrinsic resistance. CAMK1D was coexpressed PD-L1 anti-PD-L1/PD-1...
Regulatory T cells (Treg) hamper anti-tumor T-cell responses resulting in reduced survival and failure of cancer immunotherapy. Among lymphoid organs, the bone marrow (BM) is a major site Treg residence recirculation. However, process governing emigration from BM into circulation remains elusive. We here show that breast patients harbour frequencies as compared to healthy individuals or blood. This was particularly case for tumor antigen-specific which were quantified by MHCII peptide loaded...
Background Cancer immunotherapeutic strategies showed unprecedented results in the clinic. However, many patients do not respond to immuno-oncological treatments due occurrence of a plethora immunological obstacles, including tumor intrinsic mechanisms resistance cytotoxic T-cell (TC) attack. Thus, deeper understanding these is needed develop successful immunotherapies. Methods To identify novel genes that protect cells from effective TC-mediated cytotoxicity, we performed genetic screening...
Abstract During their final maturation in the medulla, semimature single-positive (SP) thymocytes downregulate activation markers and subsequently exit into periphery. Although CD4+ SP cells are sensitive to negative selection, timing of when selection occurs CD8 lineage remains elusive. We show that abundance terminally matured CD8+ adult thymus is modulated by genetic background. Moreover, BALB/c mice, frequency cells, but not present thymus, varies depending on age. In mice lacking...
<b><i>Background:</i></b> Allergic asthma is a Th2-type chronic inflammatory disease of the lung. It characterized by infiltration eosinophils, neutrophils, mast cells and T lymphocytes into airways. Th2 cytokines like interleukin (IL)-4, IL-5 chemokines eotaxin are increased in asthmatic response. The processing presentation exogenous antigens important sensitization to an allergen. Cathepsin E (Ctse) intracellular aspartic endoprotease which expressed immune...
In this prospective study, we examined postoperative follow-up and preoperative IFN-γ T cell responses against 14 non-small lung cancer (NSCLC)-associated antigens in the blood of 51 patients with NSCLC, 7 benign pulmonary tumors, 10 tumor-free by enzyme-linked immunospot assay. The phenotype function cells specific for tumor-associated (TAAs) or tumor tissue 9 NSCLC were characterized detail using TNF-α, IL-2, cytokine capture assays. We found that circulating TAA-specific significantly...
The efficacy of cancer immunotherapy may be improved by increasing the number circulating tumor-reactive T cells. bone marrow is a priming site and reservoir for such characteristics marrow-derived cells are poorly understood in patients with non-small-cell lung (NSCLC). To compare responsiveness tumor antigen-reactive from matched peripheral blood samples resectable NSCLC, we used flow cytometry, cytokine capture assays enzyme-linked immunospot to examine 14 antigens NSCLC or benign tumors...
Dendritic cells (DCs) are essential for the generation and modulation of cell-mediated adaptive immunity against infections. DC-based vaccination involves transplantation ex vivo-generated DCs loaded with antigen in vitro, but remains limited by number autologous or allogeneic cells. While vitro expansion differentiation hematopoietic stem (HSCs) into seems to be most viable alternative overcome this problem, complexity HSC has posed significant limitations clinical application. We...
Abstract High regulatory T cell (Treg) infiltration in breast tumors is associated with reduced survival. However, the source of tumor infiltrating Treg and signals underlying their migration from lymphoid organs to tissue remain elusive. We here demonstrate that pronounced human correlates a selective reduction antigen specifc bone marrow. Using MHC-II peptide tetramers we furthermore show specific marrow selectively express Sphingosine-1-phosphate receptor 1 (S1P1), mediates egress. S1P1...
Abstract High regulatory T cell (Treg) infiltration in breast tumors is associated with reduced survival. However, the source of tumor infiltrating Treg and signals underlying their migration from lymphoid organs to tissue remain elusive. We here demonstrate that pronounced human correlates a selective reduction antigen specifc bone marrow. Furthermore using MHC-II peptide tetramers we show specific marrow selectively express egress receptor Sphingosine-1-phosphate 1 (S1P1) CCR2. S1P1 CCR2...
<p>Supplementary Figure Legends</p>
<p>Graphical representation of IFN-� ELISpots using peripheral blood mononuclear T cells, co-cultivated with dendritic pulsed autologous tumor lysate fractions (A) the first (1st) PF2D dimension and corresponding (B) second (2nd) patients NCH1390, NCH612, NCH519a. Solid line represents mean background negative control (PBL). F: fraction, PBL: lymphocytes (*, p < 0.05; **, 0.01; ***, 0.001)</p>
<p>Representative images of immunohistochemical stainings the isotype controls IgG and IgG1 in normal brain (NB) tissues, astrocytomas (WHO{degree sign}II: n = 10; WHO{degree sign}III: 10), oligodendrogliomas 10). Scale bar: 50 µm.</p>
<p>Peptide information of potential T cell target antigens, tested by IFN-γ ELISpot</p>
<p>IFN-� ELISpot raw data to validate antigen immunogenicity in patients of origin. Antigens with a significant increased (grey bars and asterisks) or 1.3-fold levels immune responses bars) were further validated bigger study sample healthy individuals lower-grade glioma patients. Solid line represents mean background negative control (IgG1). (*, p < 0.05; **, 0.01; ***, 0.001)</p>
<p>(A) Applied gating strategy (one representative patient, NCH645) for the expression analysis of tumor-associated antigens in IDHmut lower-grade glioma and secondary glioblastoma GSCs, analyzed by flow cytometry regard to an adequate isotype control. (B) Fluorescence intensity measurements control antigen expressing (positive) GSC population, showing counts percentage [%] over mean PE-intensity.(C) Gating strategy, including markers pacific orange (PO), CD3, CD8, used quantification...
<p>(A) Significantly increased immune responses in IDHmut lower-grade glioma patients (P) vs. healthy donors (HD) seen for the potential T-cell target antigens CRKII, CFL1, CNTN1, NME2, and TKT. Homogenous levels of stimulation while comparing IFN-� spot numbers among astrocytomas (red) oligodendrogliomas (blue) to a certain TAA as well (B) total response. (C) ELISpot raw data showing count / 1x105 T-cells upon with autologous dendritic cells loaded (CRKII, or TKT, black bar)...
<p>(A) IFN-� ELISpot raw data of all HLA-A*02:01 patients analyzed (n = 7) showing the spots / 1x105 T-cells for patient cells against TAAs vs. negative control (human immunodeficiency virus (HIV) gag/pol, 9 amino acids). Grey bars indicate a significantly increased immunogenicity compared to (solid line). (B) Homogenous levels stimulation while comparing total immune response by mean spot numbers among astrocytomas (red) and oligodendrogliomas (blue) certain reactive epitope....
<p>Representative multicolor stainings of CFL1, CRKII, NME2, and CNTN1 on acetone-fixed cryosections with markers for common cell types in IDHmut LGGs: anti-GFAP (tumor cells, #Z0334, DAKO), anti-CD68 (microglia/ macrophages, #M0718, anti-CD31 (endothelial #223609, BD Pharmingen). Detection was performed by using fluorochrom-conjugated secondary antibodies (anti-mouse AF647 (#A-21463, Invitrogen), anti-rabbit AF555 (#A-21428, DAPI (#D1306, ThermoFisher), the Zenon AF488 mouse IgG1...
<p>Clinical data of IDHmut LGG patients</p>