A5040676467- Cancer Immunotherapy and Biomarkers
- Cannabis and Cannabinoid Research
- Immune cells in cancer
- Pregnancy and preeclampsia studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Receptor Mechanisms and Signaling
- Reproductive System and Pregnancy
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Pancreatic function and diabetes
- Lung Cancer Research Studies
- Chemokine receptors and signaling
- RNA modifications and cancer
- Neonatal Respiratory Health Research
- Preterm Birth and Chorioamnionitis
- Lung Cancer Treatments and Mutations
- MicroRNA in disease regulation
- Gestational Diabetes Research and Management
- Cancer-related molecular mechanisms research
- Cell Adhesion Molecules Research
- Eosinophilic Esophagitis
- Sleep and Wakefulness Research
- Tryptophan and brain disorders
- Cancer, Hypoxia, and Metabolism
Medical University of Graz
2016-2025
BioTechMed-Graz
2021-2024
University of Graz
2021
Fred Hutch Cancer Center
2014-2019
Cancer Research Center
2019
Clinical Research Management
2018
Seattle Institute for Biomedical and Clinical Research
2017
GlaxoSmithKline (United Kingdom)
2013
Abstract The response rate to immune checkpoint inhibitor therapy for non-small-cell lung cancer (NSCLC) is just 20%. To improve this figure, several early phase clinical trials combining novel immunotherapeutics with blockade have been initiated. Unfortunately, these designed without a strong foundational knowledge of the landscape present in NSCLC. Here, we use flow cytometry panel capable measuring 51 cell populations comprehensively identify composition and function results show that...
Gliomas harboring mutations in isocitrate dehydrogenase 1/2 (IDH1/2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time than wild-type IDH1/2 (wtIDH1/2) tumors. Although there are many factors underlying differences between these two tumor types, immune-related cell content potentially important contributors. In order to investigate role of IDH immune response, we created a syngeneic pair mouse model for mutant IDH1 (muIDH1) wtIDH1 gliomas...
BackgroundLung eosinophilia is a hallmark of asthma, and eosinophils are believed to play crucial role in the pathogenesis allergic inflammatory diseases. Short-chain fatty acids (SCFAs), such as acetate, propionate, butyrate, produced high amounts gastrointestinal tract by commensal bacteria can be absorbed into bloodstream. Although there recent evidence that SCFAs beneficial asthma models, effect on has remained elusive.ObjectiveThe was investigated human eosinophil function mouse model...
Immune checkpoint inhibitor (ICI) treatment has recently become a first-line therapy for many non–small cell lung cancer (NSCLC) patients. Unfortunately, most NSCLC patients are refractory to ICI monotherapy, and initial attempts address this issue with secondary therapeutics have proven unsuccessful. To identify entities precluding CD8+ T accumulation in process, we performed unbiased analyses on flow cytometry, gene expression, multiplexed immunohistochemical data from patient cohort. The...
The NAD + precursor nicotinamide improves diastolic dysfunction caused by aging, hypertension, or metabolic syndrome in rodents.
Although GPR55 is potently activated by the endogenous lysophospholipid, L-alpha-lysophosphatidylinositol (LPI), it also thought to be sensitive a number of cannabinoid ligands, including prototypic CB1 receptor antagonists AM251 and SR141716A (Rimonabant). In this study we have used range functional assays compare pharmacological activity selected AM251, AM281 with LPI in HEK293 cell line engineered stably express recombinant, human GPR55.We evaluated Ca(2+) signalling, stimulation...
IPF is a progressive lung disorder characterized by fibroblast proliferation and myofibroblast differentiation. Although neutrophil accumulation within lungs has been negatively correlated with outcomes, the role played neutrophils in fibrosis remains poorly understood. We have demonstrated previously that NE promotes cancer cell hypothesized it may similar effect on fibroblasts. In current study, we show NE(-/-) mice are protected from asbestos-induced fibrosis. displayed reduced content...
Abstract Lung cancer, the leading cause of cancer-related deaths worldwide, is a heterogeneous disease comprising multiple histologic subtypes that harbor disparate mutational profiles. Immune-based therapies have shown initial promise in treatment lung cancer patients but are limited by low overall response rates. We sought to determine whether host immune dictated, at least part, and genetic differences, because such correlations would important clinical ramifications. Using mouse models...
Heteromerization of GPCRs is key to the integration extracellular signals and subsequent cell response via several mechanisms including heteromer-selective ligand binding, trafficking and/or downstream signalling. As lysophosphatidylinositol GPCR 55 (GPR55) has been shown affect function cannabinoid receptor subtype 2 (CB2 receptor) in human neutrophils, we investigated possible heteromerization CB2 receptors with GPR55.The direct interaction GPR55 heterologously expressed HEK293 cells was...
T cells specific for neoantigens encoded by mutated genes in cancers are increasingly recognized as mediators of tumor destruction after immune checkpoint inhibitor therapy or adoptive cell transfer. Unfortunately, most result from random mutations and patient specific, some contain few to serve potential antigens. We describe a with stage IV acral melanoma who achieved complete response following transfer tumor-infiltrating lymphocytes (TILs). Tumor exome sequencing surprisingly revealed...
Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are interrelated diseases with substantial mortality, the pathogenesis of both involves aberrant immune functioning.
T cells specific for neoantigens encoded by mutated genes in cancers are increasingly recognized as mediators of tumor destruction after immune-checkpoint inhibitor therapy or adoptive cell transfer. Much the focus has been on identifying epitopes presented to CD8+ class I MHC. However, CD4+ II MHC-restricted have shown an important role antitumor immunity. Unfortunately, vast majority cancer patients result from random mutations and patient-specific. Here, we screened blood 5 non-small lung...
The G protein–coupled receptor 55 (GPR55) is a lysophosphatidylinositol (LPI) that also responsive to certain cannabinoids. Although GPR55 has been implicated in several (patho)physiologic functions, its role remains enigmatic owing mainly the lack of selective antagonists. Here we show compound CID16020046 ((4-[4-(3-hydroxyphenyl)-3-(4-methylphenyl)-6-oxo-1<i>H</i>,4<i>H</i>,5<i>H</i>,6<i>H</i>-pyrrolo[3,4-c]pyrazol-5-yl] benzoic acid) antagonist. In yeast cells expressing human GPR55,...
Background and Purpose Tumour cell migration adhesion constitute essential features of metastasis. G‐protein coupled receptor 55 (GPR55), a lysophospholipid receptor, has been shown to play an important role in carcinogenesis. Here, we investigated the involvement GPR55 metastasis colon cancer cells. Experimental Approach Adhesion assays using highly metastatic line HCT116 vivo assay liver were performed. The antagonist CID16020046, cannabidiol, putative siRNA used block activity Key Results...
The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid 1 (CB1R) are co-expressed in many tissues, predominantly central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- heteromers initiate distinct signaling pathways. Recently, several synthetic CB1 inverse agonists/antagonists, such as SR141716A, AM251, AM281, were reported to activate GPR55. Of these, SR141716A was marketed a promising anti-obesity drug, but withdrawn from market because of...
In many types of cancer, presence eosinophils in tumors correlate with an improved disease outcome. line this, activated have been shown to reduce tumor growth colorectal cancer (CRC). Interleukin (IL)-33 has recently emerged as a cytokine that is able inhibit the development through and other cells microenvironment thereby positively influencing progress. Here, we asked whether are involved effects IL-33 on CRC.In models CT26 cell engraftment colitis-associated CRC, was reduced after...
Cannabinoid (CB) receptors (CB 1 and CB 2 ) are expressed on cancer cells their expression influences carcinogenesis in various tumor entities. Cells of the microenvironment (TME) also express receptors, however, role development is still unclear. We, therefore, investigated TME-derived a model non-small cell lung (NSCLC). Leukocytes TME mouse human NSCLC with showing higher than . In model, using - -/- -knockout mice, only deficiency , but not resulted reduction burden vs. wild type (WT)...
lo , have a specific transcriptome, and proliferate in situ d decBAMs are inefficient APCs, induce Tregs, secrete IL-