A5089657026- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Cancer-related gene regulation
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Epigenetics and DNA Methylation
- T-cell and B-cell Immunology
- Sociology and Education Studies
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- Drug Transport and Resistance Mechanisms
- Cancer Research and Treatments
- Tryptophan and brain disorders
- RNA modifications and cancer
- German Colonialism and Identity Studies
- ATP Synthase and ATPases Research
- Adipokines, Inflammation, and Metabolic Diseases
- Linguistic Education and Pedagogy
- Mitochondrial Function and Pathology
- Psychology, Coaching, and Therapy
- Pharmacological Effects and Toxicity Studies
- Biochemical and Molecular Research
- Single-cell and spatial transcriptomics
- Histone Deacetylase Inhibitors Research
University Hospital Regensburg
2016-2025
Universität Hamburg
2023
Max Planck Institute for Comparative and International Private Law
2023
Deutsche Nationalbibliothek
2023
University of Regensburg
2013-2020
Universitätsklinikum Erlangen
2016
Friedrich-Alexander-Universität Erlangen-Nürnberg
2010-2015
Singer (United States)
2010
Ri.MED
2009
The University of Western Australia
2008
•Glycolytic index in melanoma negatively correlates with response to anti-PD1 therapy•Blocking lactate transport or knock out of glycolytic genes improves checkpoint therapy•Diclofenac blocks the transporters MCT1 and MCT4 a COX-independent manner•Inhibition glycolysis by MCT blockade does not impede T cell function SummaryTumor-derived lactic acid inhibits natural killer (NK) and, thereby, tumor immunosurveillance. Here, we report that patients high expression glycolysis-related show worse...
Macrolides may cause severe drug interactions due to the inhibition of metabolizing enzymes. Transporter-mediated uptake drugs into cells [e.g., by members human organic anion transporting polypeptide (OATP) family] is a determinant disposition and prerequisite for subsequent metabolism. However whether macrolides are also inhibitors transporters, thereby providing an additional mechanism interactions, has not been systematically studied. The OATP family OATP1B1 OATP1B3 mediate endogenous...
Many tumor cells are characterized by a dysregulated glucose metabolism associated with increased glycolysis in the presence of oxygen ("Warburg Effect"). Here, we analyzed for first time possible link between and immune cell infiltration renal carcinoma (RCC). RCC specimens revealed highly significant increase expression lactate dehydrogenase A (LDHA) glucose-transporter 1 (GLUT-1) compared to corresponding normal kidney tissue on mRNA level. Accordingly, lines different origin such as RCC,...
Obesity promotes adipose tissue inflammation and leads to impaired local but also systemic immune cell homeostasis. This chronic low-grade plays a significant role in the development of obesity-associated secondary diseases such as metabolic associated fatty liver disease or cancer. The spleen central organ regulation is anatomically directly connected visceral via portal vein circulation. However, inter-organ crosstalk linkage between obesity-induced systemic, hepatic splenic dysregulation...
The organic cation transporters 1 (OCT1) and 2 (OCT2) mediate drug uptake into hepatocytes renal proximal tubular cells, respectively. Multidrug toxin extrusion protein (MATE1) is a major component of subsequent export bile urine. However, the functional interaction OCTs MATE1 for transcellular transport oral antidiabetic metformin or 1-methyl-4-phenylpyridinium (MPP(+)) has not fully been characterized.Single-transfected Madin-Darby canine kidney (MDCK) cells as well double-transfected...
Non-steroidal anti-inflammatory drugs such as diclofenac exhibit potent anticancer effects. Up to now these effects were mainly attributed its classical role COX-inhibitor. Here we show novel COX-independent of diclofenac. Diclofenac significantly diminished MYC expression and modulated glucose metabolism resulting in impaired melanoma, leukemia, carcinoma cell line proliferation vitro reduced melanoma growth vivo. In contrast, the non-selective COX inhibitor aspirin COX-2 specific NS-398...
The strong link between T‐cell metabolism and effector functions is well characterized in the murine system but hardly investigated human T cells. Therefore, we analyzed glycolytic mitochondrial activity correlation to function activated CD4 CD8 Glycolysis was barely detectable upon stimulation accelerated beyond 24 h, whereas elevated immediately both populations. Glucose deprivation or restriction reduced proliferation, had only a transient impact on “on‐blast formation” no viability,...
Green tea catechins inhibit the function of organic anion transporting polypeptides (OATPs) that mediate uptake a diverse group drugs and endogenous compounds into cells. The present study was aimed at investigating effect green its most abundant catechin epigallocatechin gallate (EGCG) on transport activity several drug transporters expressed in enterocytes, hepatocytes renal proximal tubular cells such as OATPs, cation (OCTs), multidrug toxin extrusion proteins (MATEs), P-glycoprotein...
Despite extensive studies on the chromatin landscape of exhausted T cells, transcriptional wiring underlying heterogeneous functional and dysfunctional states human tumor-infiltrating lymphocytes (TILs) is incompletely understood. Here, we identify gene-regulatory landscapes in a wide breadth CD8+ TIL covering four cancer entities using single-cell profiling. We map enhancer-promoter interactions TILs by integrating accessibility with RNA-seq data from tumor-entity-matching samples...
The immunosuppressive tumor microenvironment represents one of the main obstacles for immunotherapy cancer. milieu is among others shaped by metabolites such as 5′-deoxy-5′-methylthioadenosine (MTA). Increased intratumoral MTA levels result from a lack MTA-catabolizing enzyme methylthioadenosine phosphorylase (MTAP) in cells and are found various entities. Here, we demonstrate that suppresses proliferation, activation, differentiation, effector function antigen-specific T without eliciting...
L-kynurenine is a tryptophan-derived immunosuppressive metabolite and precursor to neurotoxic anthranilate quinolinate. We evaluated the stereoisomer D-kynurenine as an therapeutic which hypothesized produce less metabolites than L-kynurenine.L-/D-kynurenine effects on human murine T cell function were examined in vitro vivo (homeostatic proliferation, colitis, cardiac transplant). Kynurenine metabolism interrogated using [13C] glucose, glutamine palmitate tracing. was measured tissues from...
Metabolic pathways regulate immune responses and disrupted metabolism leads to dysfunction disease. Coronavirus disease 2019 (COVID-19) is driven by imbalanced responses, yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 87 patients with confirmed SARS-CoV-2 infection, 6 critically ill non–COVID-19 patients, 47 uninfected controls, we found an immunometabolic dysregulation progressed COVID-19. Specifically, T cells, monocytes, granulocytes exhibited...
Nadolol is a nonmetabolized β-adrenoceptor antagonist and substrate of OATP1A2, but not OATP2B1. However, other drug transporters involved in translocation nadolol have been characterized detail. We therefore investigated as potential the hepatic uptake OATP1B1, OATP1B3, OCT1 renal OCT2, MATE1, MATE2-K expressed HEK cells. Moreover, importance P-glycoprotein (P-gp) for transport was studied using double transfected MDCK-OCT1-P-gp transported by OATP1B1 OATP1B3. In contrast, significantly...
Genetic alterations in tumor cells provide promising targets for antitumor therapy. Recently, loss of methylthioadenosine phosphorylase (MTAP), a deletion frequently occurring cancer, has been shown to create vulnerability the inhibition protein arginine methyltransferase 5 (PRMT5). MTAP deficiency leads accumulation (MTA), which reduces PRMT5 activity, and thus, sensitizes selective inhibitors (PRMT5i). PRMT5i are investigated as new strategy selectively kill MTAP-deficient by blocking...
Background: Melanoma and squamous cell carcinoma of the skin are characterized by an altered glucose metabolism, but little is known about metabolic changes in precancerous lesions such as actinic keratosis (AK). Here, we studied central carbon metabolism immune infiltrate before, under, 4 weeks after treatment with topical diclofenac (Solaraze®). Methods: This study was designed a prospective, randomized, controlled, monocentric investigation (ClinicalTrials.gov Identifier: NCT01935531)....
Mutations in isocitrate dehydrogenase (IDH) or a reduced expression of L-2-hydroxyglutarate (HG)-dehydrogenase result accumulation D-2-HG L-2-HG, respectively, tumor tissues. and L-2-HG have been shown to affect T-cell differentiation activation; however, effects on human myeloid cells not investigated so far. In this study we analyzed the impact activation maturation monocyte-derived dendritic (DCs). 2-HG was taken up by DCs had no cell viability but diminished CD83 after...