A5086617153- Immune cells in cancer
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- Mast cells and histamine
- CAR-T cell therapy research
- Cell Adhesion Molecules Research
- Nanoplatforms for cancer theranostics
- T-cell and B-cell Immunology
- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- Chemokine receptors and signaling
- Cancer Research and Treatments
- Phagocytosis and Immune Regulation
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- Toxic Organic Pollutants Impact
- Autophagy in Disease and Therapy
- Glycosylation and Glycoproteins Research
- Osteoarthritis Treatment and Mechanisms
- Reproductive System and Pregnancy
- Fungal Biology and Applications
- Acute Myeloid Leukemia Research
University Hospital of Zurich
2024
Boehringer Ingelheim (Austria)
2015-2023
Boehringer Ingelheim (Germany)
2021
Novartis (Austria)
2005-2008
University of Vienna
2006
Medical University of Vienna
2005
Forschungs- und Beratungsstelle Arbeitswelt
1995
The tumour microenvironment (TME) shapes disease progression and influences therapeutic response. Most aggressive solid tumours have high levels of myeloid cell infiltration, namely associated macrophages (TAM). Recapitulation the interaction between different cellular players TME, along with extracellular matrix (ECM), is critical for understanding mechanisms underlying progression. This particularly holds true prediction response(s) to standard therapies interrogation efficacy...
Abstract The ruthenium complex sodium trans-[tetrachloridobis(1H-indazole)ruthenate(iii)] (KP1339/IT-139) showed preclinical activity in a variety of vivo tumor models including highly predictive colon cancer model. compound has entered clinical trials, where patients experienced disease stabilization accompanied by mild side effects. KP1339, GRP78 inhibitor, disrupts endoplasmic reticulum (ER) homeostasis leading to cell death. PERK/eIF2α-branch the ER plays an essential role cascade events...
Colorectal cancer (CRC) accounts for about 10% of deaths worldwide. Colon carcinogenesis is critically influenced by the tumor microenvironment. Cancer associated fibroblasts (CAFs) and macrophages (TAMs) represent major components TAMs promote progression, angiogenesis tissue remodeling. However, impact molecular crosstalk cells (TCs) with CAFs on monocyte recruitment their phenotypic conversion not known in detail so far. In a 3D human organotypic CRC model, we show that normal colonic are...
IL-5, which is produced mainly by activated T cells and allergically triggered mast cells, a major survival differentiation factor for eosinophils, therefore, of relevance to diseases associated with this type cell infiltration, most importantly asthma. In study, we have examined the transcriptional regulation human IL-5 in mouse line, CPII, stimulated IgE Ag. We report that an inducible activity region between -177 -80, constitutive -80 -70, promoter gene, are both necessary activation. A...
IL-21 is a cytokine produced by CD4+ T cells that has been reported to regulate human, as well as, mouse and NK cell function inhibit Ag-induced IgE production B cells. In the present study, we show human rIL-21 strongly enhances both CD19+ CD27- naive, CD27+ memory cells, stimulated with anti-CD40 mAb rIL-4 it promotes proliferative responses of these However, does not significantly affect rIL-4-induced Cepsilon promoter activation in gene reporter assay, nor germline mRNA expression...
We established co-cultures of invasive or non-invasive NSCLC cell lines and various types fibroblasts (FBs) to more precisely characterize the molecular mechanism tumor-stroma crosstalk in lung cancer. The HGF-MET-ERK1/2-CREB-axis was shown contribute onset phenotype Calu-1 with HGF being secreted by FBs. Differential expression analysis respective mono- revealed an upregulation NFκB-related genes exclusively Calu-1. Cytokine Array- ELISA-based characterization "cytokine fingerprints"...
The chemokine CCL23 is primarily expressed in cells of the myeloid lineage but little information about its regulation available. In this study, it demonstrated that IL-4 and IL-13 induced expression human peripheral blood monocytes. GM-CSF had no effect on own synergized with IL-4, not IL-13. promoter reporter gene constructs were sensitive to stimulation presence transcription factor STAT6. A canonical STAT6 binding site region was critical for IL-4-inducible phenotype because plasmids a...
The neuropeptide CGRP, acting through the G-protein coupled receptor CALCRL and its coreceptor RAMP1, plays a key role in migraines, which has led to clinical development of several inhibitory compounds. Recently, high
During allergic lung inflammation dendritic cells (DCs) direct the generation and function of effector T-helper type 2 cells. not only orchestrate inflammatory processes in tissue by inducing accumulation activation proinflammatory but also induce IgE production B Thus, inhibitors DC should have therapeutic benefits patients with allergies.VAF347, a novel low molecular weight immunomodulator, is described acts as an antiinflammatory compound dual mode action.VAF347 inhibited human...
Very recently, an AP3-like transcription factor regulating the chemokine gene MARC and NF-AT family member IL-5 were first components of repertoire to be described as activated in mast cells after allergic triggering. In this study, we show that with respect cross-competition a gel shift analysis using consensus oligonucleotide binding site, antigenicity recently generated serum against T cell NF-AT, sensitivity macrolide immunosuppressants, activity on promoter is indistinguishable from for...
While it was recently shown that activation of dendritic cells (DC) results in the production a number cytokines, signal pathways and transcription factors involved this process have not been described. To address issue we compared events resulting human TNF-alpha promoter occurring fetal cell line 18 (DC18) with those well-characterized murine mast CPII. As stimuli employed protein kinase C inducer, PMA, Ca2+ ionophore, ionomycin, both which are known to activate large variety intracellular...
Antibody-mediated cancer immunotherapy targets inhibitory surface molecules, such as PD1, PD-L1, and CTLA-4, aiming to re-invigorate dysfunctional T cells. We purified characterized tumor-infiltrating lymphocytes (TILs) their patient-matched non-tumor counterparts from treatment-naïve NSCLC patient biopsies evaluate the effect of PD1 expression on functional molecular profiles tumor-resident show that PD1+ CD8+ TILs have elevated transcriptional regulator ID3 cytotoxic potential CD8 cells...
Phosphatidylinositol-3-kinase (PI3-kinase) comprises an essential component in a number of signaling cascades, primarily the growth factor type. Two specific inhibitors, wortmannin and demethoxyviridin (DMV), are widely used to block via this molecule link certain receptors PI3-kinase pathway.We have studied extent involvement events by Fc epsilonRI mast cells using mouse cell line as model system. This was done beta-hexosaminidase release assays, leukotriene ELISA, transient transfections...
// David J. Lamb 1 , Aleksander Rust 2 Albin Rudisch 3 Tobias Glüxam 4 Nathalie Harrer Herwig Machat Ingrid Christ Florian Colbatzky 5 Andreas Wernitznig Annika Osswald 6 and Wolfgang Sommergruber 7 Immunology & Respiratory, Boehringer Ingelheim Pharma GmbH Co. KG, 88397 Biberach an der Riß, Germany Cancer Biology Genetics Program, Memorial Sloan Kettering Center, New York, NY 10065, USA Cell Signalling, RCV Co A-1121 Vienna, Austria Department of Medicine I, Comprehensive Medical University...
Although T cell abundance in solid tumours is associated with better outcomes, it also correlates a stroma-mediated source of immune suppression driven by TGFβ1 and poor overall survival. Whether this observed non-small lung cancer (NSCLC) unknown. We utilized molecular analysis The Cancer Genome Atlas (TCGA) NSLCC cohort to correlate activation (IA) gene expression extracellular matrix/stromal (ECM/stromal) patient In an independent NSCLC samples, we used flow cytometry identify mesenchymal...
Abstract Acute myeloid leukemia (AML) derives from hematopoietic stem and progenitor cells (HSPCs). To date, no AML‐exclusive, non‐HSPC‐expressed cell‐surface target molecules for AML selective immunotherapy have been identified. Therefore, to still apply surface‐directed in this disease setting, time‐limited combined immune‐targeting of healthy HSPCs, followed by cell transplantation (HSCT), might be a viable therapeutic approach. explore this, we generated recombinant single‐chain variable...
Abstract Chemotherapeutic drugs exert their activity by directly killing tumor cells through a variety of cellular targets eventually leading to apoptosis. Apoptosis is regarded as non-inflammatory and non-immunogenic, however, recent data confirm that the induction damage-associated molecular patterns dying cancer treated with certain chemotherapeutic agents, such oxaliplatin, lead recognition immune system, result in dendritic cell maturation responses, mechanism described Immunogenic Cell...
<h3>Background</h3> The tumor microenvironment is a highly complex and continuously adapting tissue. crosstalk between the different cell types non-cellular components difficult to monitor, specifically with aim identify possible novel anticancer drug targets. <h3>Methods</h3> We co-cultivated two human NSCLC lines, H1437 Calu-1, fetal dermal fibroblasts (HDF) or murine lung (muLF) monocytes in combinations of co- triple cultures. To discriminate phenotypic events driven by cell-cell contact...
<h3>Background</h3> The mechanisms underlying the spatiotemporal development of tumor microenvironment (TME) present a challenge in evaluating drug efficacy and molecular biology. 3D culture systems are an indispensable tool to delineate dynamic interplay between host microenvironment. <h3>Methods</h3> Four human PDX (patient derived xenograft) models, LXFA923, LXFA289, LXFL1121 LXFL1674, two murine, KP1 KP4, non-small cell lung cancer (NSCLC) models were cultivated under different...
Introduction Tumour initiation, progression and treatment are influenced by its microenvironment (TME). Chronic inflammation is linked to cancer in diverse pathologies most aggressive solid tumours, including non-small cell lung carcinoma (NSCLC), have high levels of immune infiltration. Tumor-associated macrophages (TAM) among the abundant infiltrating cells, with tumour-promoting effects such as induction proliferation, angiogenesis evasion from adaptive immunity. Recapitulation...
Introduction Tumor-macrophage (Mφ) crosstalk has been extensively studied and both cytokine networks cell-cell interactions at the tumour site directly impact therapeutic outcome. Tumour modelling brings up tools that can be explored to uncover targets for intervention. We developed a model system based on co-culture of lung spheroids, fibroblasts Mφ, which emulate aspects microenvironment dynamics. In co-culture, Mφ infiltrate mass display promoting features, e.g. secretion M2-like...