A5091558431- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Nanoplatforms for cancer theranostics
- Immune Cell Function and Interaction
- Brain Metastases and Treatment
- Chemokine receptors and signaling
- CAR-T cell therapy research
- Immune Response and Inflammation
- Extracellular vesicles in disease
- Inflammation biomarkers and pathways
- Melanoma and MAPK Pathways
- Inflammatory Biomarkers in Disease Prognosis
- Computational Drug Discovery Methods
- T-cell and B-cell Immunology
- Histone Deacetylase Inhibitors Research
- S100 Proteins and Annexins
- Cancer Cells and Metastasis
- Monoclonal and Polyclonal Antibodies Research
- Advanced Nanomaterials in Catalysis
- Neuroinflammation and Neurodegeneration Mechanisms
- CRISPR and Genetic Engineering
- 3D Printing in Biomedical Research
- Cancer, Stress, Anesthesia, and Immune Response
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
German Cancer Research Center
2016-2025
Heidelberg University
2016-2025
University Hospital Heidelberg
2015-2024
University Medical Centre Mannheim
2015-2024
Charles River Laboratories (Netherlands)
2021
John Wiley & Sons (United States)
2021
Hudson Institute
2021
Medizinische Fakultät Mannheim
2014-2018
Heidelberg University
2014-2015
University Medical Center
2013-2015
We hypothesized that the combination of oncolytic virotherapy with immune checkpoint modulators would reduce tumor burden by direct cell lysis and stimulate antitumor immunity. In this study, we have generated attenuated Measles virus (MV) vectors encoding antibodies against CTLA-4 PD-L1 (MV-aCTLA-4 MV-aPD-L1). characterized in terms growth kinetics, antibody expression, cytotoxicity vitro. Immunotherapeutic effects were assessed a newly established, fully immunocompetent murine model...
The antitumor effects of paclitaxel are generally attributed to the suppression microtubule dynamics resulting in defects cell division. New data demonstrated that ultralow noncytotoxic concentrations, modulated immune cells vitro activity small Rho GTPases, key regulators intracellular actin dynamics. However, immunomodulatory properties vivo have not been evaluated. In this study, using ret transgenic murine melanoma model, which mimics human cutaneous melanoma, we tested dose on functions...
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human neoplasms with extremely poor prognosis and a low survival rate. Immunosuppressive cell populations, e.g . regulatory T cells (Treg), appear to be important in PDAC, contributing patient's prognosis. Therefore, we investigated PDAC microenvironment focus on conventional view their potential therapeutic importance. We found that tumors from murine Panc02 orthotopic model were infiltrated high numbers Treg. Remarkably,...
Chronic inflammation is considered to be one of the hallmarks for tumor initiation and progression. Moreover, a long-term production accumulation inflammatory factors lead local systemic immunosuppression associated with cancer However, correlation between mediators, immunosuppressive cells clinical outcome malignant melanoma patients was poorly investigated. In this study, we performed complex analysis various factors, myeloid-derived suppressor (MDSCs) regulatory T (Tregs) in peripheral...
Inducible NO synthase (iNOS) is a hallmark of chronic inflammation that also overexpressed in melanoma and other cancers. Whereas iNOS known effector myeloid-derived suppressor cell (MDSC)-mediated immunosuppression, its pivotal position at the interface cancer makes it an attractive candidate regulator MDSC recruitment. We hypothesized tumor-expressed controls accumulation acquisition suppressive activity melanoma. CD11b(+)GR1(+) derived from mouse bone marrow cells cultured presence...
Abstract Accumulation of myeloid-derived suppressor cells (MDSC) in melanoma microenvironment is supported by chemokine receptor/chemokine signaling. Although different chemokines were suggested to be involved this process, the role CCR5 and its ligands not established. Using a Ret transgenic mouse model, we found an accumulation CCR5+ MDSCs lesions associated with both increased concentrations tumor progression. Tumor-infiltrating displayed higher immunosuppressive activity than their CCR5−...
Myeloid cells play a key role in the outcome of anti-tumor immunity and response to anti-cancer therapy, since tumor microenvironment they may exert both stimulatory inhibitory pressures on proliferative, angiogenic, metastatic, immunomodulating potential cells. Therefore, understanding mechanisms myeloid regulatory cell differentiation is critical for developing strategies therapeutic reversal derived suppressor (MDSC) accumulation tumor-bearing hosts. Here, using an vitro model system,...
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:...
Tumor cell-derived extracellular vesicles (EV) convert normal myeloid cells into myeloid-derived suppressor (MDSC), inhibiting antitumor immune responses. Here, we show that EV from Ret mouse melanoma upregulate the expression of programmed cell death ligand 1 (PD-L1) on immature (IMC), leading to suppression T-cell activation. PD-L1 and immunosuppressive potential EV-generated MDSC were dependent Toll-like receptors (TLR). IMC Tlr4-/- mice failed increase immunosuppression with Ret-EV...
Tumor progression is often associated with chronic inflammation in the tumor microenvironment, which mediated by numerous cytokines, chemokines and growth factors produced cancer stroma cells. All these mediators support development immunosuppression autocrine and/or paracrine ways. Neutralization of inflammatory conditions can lead to restoration anti-tumor immune responses. Among cells infiltrating tumors, myeloid-derived suppressor (MDSCs) represent one most important players mediating...
Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers in world. PDAC cells activate tumor-specific immune responses but simultaneously trigger a strong immunosuppression. We showed that produce high amount chronic inflammatory mediators and tumors build an immunosuppressive cytokine milieu, which correlates with tumor progression. observed low frequency dendritic (DC) pronounced accumulation macrophages myeloid-derived suppressor (MDSC) murine tumors. A MDSC has...
Background Myeloid-derived suppressor cells (MDSC) play a major role in the immunosuppressive melanoma microenvironment. They are generated under chronic inflammatory conditions characterized by constant production of cytokines, chemokines and growth factors, including IL-6. Recruitment MDSC to tumor is mediated interaction between chemokine receptors, particular C–C receptor (CCR)5. Here, we studied mechanisms CCR5 upregulation increased function + MDSC. Methods The immortalized myeloid...
Malignant melanoma is the deadliest of skin cancers. Melanoma frequently metastasizes to brain, resulting in dismal survival. Nevertheless, mechanisms that govern early metastatic growth and interactions disseminated cells with brain microenvironment are largely unknown. To study hallmarks niche formation, we established a transplantable model spontaneous metastasis immunocompetent mice developed molecular tools for quantitative detection micrometastases. Here demonstrate micrometastases...
Eosinophils have been identified as a prognostic marker in immunotherapy of melanoma and suggested to contribute anti-tumor host defense. However, the influence immune checkpoint inhibitors (ICI) on eosinophil population is poorly studied. Here, we applied routine laboratory tests, multicolor flow cytometry, RNA microarray analysis, bio-plex assay analyze circulating eosinophils related serum inflammatory factors 32 patients treated with pembrolizumab or combination nivolumab ipilimumab. We...
Background Myeloid-derived suppressor cells (MDSCs) represent a negative prognostic factor in malignant melanoma. These are generated under chronic inflammatory conditions typical of cancer. The transcription signal transducer and activator 3 (STAT3) orchestrates MDSC accumulation acquisition immunosuppressive properties. Here we studied STAT3 inhibition by Napabucasin as way to block activity its potential treat Methods In vitro murine primary from melanoma-bearing mice were used...