- Immunotherapy and Immune Responses
- interferon and immune responses
- Immune Cell Function and Interaction
- Immune cells in cancer
- Cancer Research and Treatments
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Immune Response and Inflammation
- Phagocytosis and Immune Regulation
- Nanoplatforms for cancer theranostics
- Inflammasome and immune disorders
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- RNA Interference and Gene Delivery
- Cytokine Signaling Pathways and Interactions
- IL-33, ST2, and ILC Pathways
- Pancreatic and Hepatic Oncology Research
- Adenosine and Purinergic Signaling
- Cancer, Hypoxia, and Metabolism
- Tryptophan and brain disorders
- Psoriasis: Treatment and Pathogenesis
- RNA modifications and cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinoids in leukemia and cellular processes
- Cardiac Ischemia and Reperfusion
Center for Integrated Protein Science Munich
2014-2021
Ludwig-Maximilians-Universität München
2012-2021
LMU Klinikum
2009-2021
German Center for Lung Research
2013-2017
University of Fribourg
2014
Helmholtz Zentrum München
2014
Roche (Switzerland)
2014
University Hospital Cologne
2014
Klinik und Poliklinik für Orthopädie, Physikalische Medizin und Rehabilitation
2014
München Klinik
2003-2014
<h3>Background</h3> The proinflammatory cytokines interleukin 1β (IL-1β) and IL-18 are central players in the pathogenesis of inflammatory bowel disease (IBD). In response to a variety microbial components crystalline substances, both processed via caspase-1-activating multiprotein complex, NLRP3 inflammasome. Here, role inflammasome experimental colitis induced by dextran sodium sulfate (DSS) was examined. <h3>Methods</h3> IL-1β production DSS studied macrophages wild-type,...
Abstract Detailed information of human B cell activation via TLR may lead to a better understanding involvement in autoimmunity and malignancy. In this study we identified fundamental difference the regulation TLR7- TLR9-mediated stimulation: whereas induction polyclonal naive proliferation by TLR7 ligands resiquimod (R848) loxoribine required presence plasmacytoid dendritic cells (PDCs), TLR9 ligand CpG was independent PDCs. We found that PDC-derived type I IFN enhanced sensitivity...
Abstract It is widely believed that generation of mature dendritic cells (DCs) with full T cell stimulatory capacity from human monocytes in vitro requires 5–7 days differentiation GM-CSF and IL-4, followed by 2–3 activation. Here, we report a new strategy for maturation monocyte-derived DCs within only 48 h culture. Monocytes acquire immature DC characteristics day 2 culture IL-4; they down-regulate CD14, increase dextran uptake, respond to the inflammatory chemokine macrophage protein-1α....
Extracellular ATP mediates numerous biological activities by interacting with plasma membrane P2 purinergic receptors. Recently, receptors have been described on dendritic cells (DC), but their functional role remains unclear. Proposed functions include improved Ag presentation, cytokine production, chemotaxis, and induction of apoptosis. We investigated the effects other receptor agonists endocytosis, phenotype, IL-12 secretion, T cell stimulatory capacity human monocyte-derived DC. found...
<b><i>Background:</i></b> Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation due to dysregulation of the mucosal immune system. The cytokines IL-1β and IL-18 appear early in their pro-forms are processed via caspase-1-activating multiprotein complex, Nlrp3 inflammasome. Previously, we reported that uptake dextran sodium sulfate (DSS) macrophages activates inflammasome Nlrp3<sup>–/–</sup> mice protected acute DSS colitis...
Abstract Deregulated TGF-β signaling in pancreatic cancer promotes tumor growth, invasion, metastasis, and a potent immunosuppressive network. A strategy for disrupting this tumor-promoting pathway is silencing by siRNA. By introducing triphosphate group at the 5′ end of siRNA (ppp-siRNA), gene can be combined with immune activation via cytosolic helicase retinoic acid-inducible I (RIG-I), ubiquitously expressed receptor recognizing viral RNA. We validated RIG-I as therapeutic target showing...
Significance IL-22 has been identified as a cancer-promoting cytokine, but its regulation in cancer tissue not addressed. Using both murine and human models, we demonstrate that cells directly induce production. We prove interleukin-1β induced by inflammasome activation is critical for IL-1β increased the activity of transcription factors lineage-committed T cells. show existence IL-22–producing Th1, Th17, Th22 tumor patients. Use clinically approved IL-1 receptor antagonist anakinra vivo...
Adoptive T cell transfer (ACT) is currently under investigation for the treatment of metastatic cancer. Recent evidence suggests that coinhibitory PD-1-PD-L1 axis plays a major role in ACT failure. We hypothesized new fusion receptor reverting PD-1-mediated inhibition into CD28 costimulation may break peripheral tolerance.Different PD-1-CD28 constructs were created and retrovirally transduced primary transgenic murine CD8(+) cells specific ovalbumin (OT-1). Cytokine release, proliferation,...
Abstract Cancer vaccines aim to induce CTL responses against tumors. Challenges for vaccine design are targeting Ag dendritic cells (DCs) in vivo, facilitating cross-presentation, and conditioning the microenvironment Th1 type immune responses. In this study, we report that ISCOM vaccines, which consist of ISCOMATRIX adjuvant protein Ag, meet these challenges. Subcutaneous injection an mice led a substantial influx activation innate adaptive effector site-draining lymph nodes (VDLNs) as well...
Abstract Cancer vaccines aim to induce antitumor CTL responses, which require cross-presentation of tumor Ag CTLs by dendritic cells (DCs). Adjuvants that facilitate vaccine are therefore key for inducing immunity. We previously reported human DCs could not efficiently cross-present the full-length cancer/testis NY-ESO-1 unless formulated as either an immune complex (NY-ESO-1/IC) or with ISCOMATRIX adjuvant. now demonstrate NY-ESO-1/ICs HLA-A2- and HLA-Cw3-restricted epitopes via a...
Abstract Regulatory T cells (Treg) mediate tolerance towards self‐antigens by suppression of innate and adaptive immunity. In cancer patients, tumor‐infiltrating FoxP3+ Treg suppress local anti‐tumor immune responses are often associated with poor prognosis. Markers that selectively expressed on may serve as targets for immunotherapy cancer. Here we show CD103, an integrin mediating lymphocyte retention in epithelial tissues, is at high levels several types murine the CT26 model colon up to...
Abstract Adjuvants are an essential component of modern vaccines and used for their ability to elicit immunity coadministered Ags. Many adjuvants in clinical development particulates, but how they drive innate adaptive immune responses remains poorly understood. Studies have shown that a number vaccine activate inflammasome pathways isolated APCs. However, the contribution activation vaccine-mediated vivo controversial. In this study, we evaluated cell ISCOMATRIX adjuvant (IMX) mice. Like...
Vaccines based on immune stimulatory complexes (ISCOM) induce T-cell responses against tumor antigen (Ag). However, are impaired in pancreatic cancer patients. We investigated the efficacy of an ISCOM vaccine a murine carcinoma model. Panc02 cells expressing OVA as model Ag were induced subcutaneously or orthotopically pancreas C57BL/6 mice. Treatment consisted containing vaccine, either used alone combination with TLR9 agonist CpG. The effectively Ag-specific CTL capable killing cells. mice...