A5074826097- Cancer Immunotherapy and Biomarkers
- Cell death mechanisms and regulation
- Autophagy in Disease and Therapy
- Cancer Genomics and Diagnostics
- interferon and immune responses
- Phagocytosis and Immune Regulation
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Cancer, Stress, Anesthesia, and Immune Response
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Quinazolinone synthesis and applications
- PARP inhibition in cancer therapy
- Immune cells in cancer
- Cancer therapeutics and mechanisms
- Chemical Reactions and Isotopes
- Monoclonal and Polyclonal Antibodies Research
- DNA Repair Mechanisms
- Advanced Breast Cancer Therapies
- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- Lung Cancer Research Studies
- Prenatal Screening and Diagnostics
- Radiomics and Machine Learning in Medical Imaging
National Center for Tumor Diseases
2024-2025
University of Duisburg-Essen
2011-2025
Essen University Hospital
2012-2025
St. Jude Children's Research Hospital
2017-2025
Deutschen Konsortium für Translationale Krebsforschung
2020-2025
West Cancer Center
2023
Institute of Immunology
2016-2020
The absence of Caspase-8 or its adapter, Fas-associated death domain (FADD), results in activation receptor interacting protein kinase-3 (RIPK3)- and mixed-lineage kinase-like (MLKL)-dependent necroptosis vivo. Here, we show that spontaneous RIPK3, phosphorylation MLKL, Caspase-8- FADD-deficient cells was dependent on the nucleic acid sensor, Z-DNA binding protein-1 (ZBP1). We genetically engineered a mouse model by single insertion FLAG tag onto N terminus endogenous MLKL (
Understanding tumor resistance to T cell immunotherapies is critical improve patient outcomes. Our study revealed a role for transcriptional suppression of the tumor-intrinsic HLA class I (HLA-I) antigen processing and presentation machinery (APM) in therapy resistance. Low HLA-I APM mRNA levels melanoma metastases before immune checkpoint blockade (ICB) correlated with nonresponsiveness poor clinical outcome. Patient-derived cells silenced escaped recognition by autologous CD8+ cells....
Abstract The efficacy of immune surveillance and antigen-specific cancer immunotherapy equally depends on the activation a sustained response targeting antigens susceptibility cells to effector mechanisms. Using functional expression cloning T-cell receptor (TCR) transgenic mice, we have identified cyclooxygenase 2/prostaglandin-endoperoxide synthase 2 (COX-2) as resistance factor against cytotoxicity induced by activated, T cells. Expressing COX-2, but not catalytically inactive COX-2...
Whether cell types exposed to a high level of environmental insults possess type-specific prosurvival mechanisms or enhanced DNA damage repair capacity is not well understood. BRN2 tissue-restricted POU domain transcription factor implicated in neural development and several cancers. In melanoma, plays key role promoting invasion regulating proliferation. Here we found, surprisingly, that rather than interacting with cofactors, instead associated response proteins directly binds PARP1...
Expression of BCL-B, an anti-apoptotic BCL-2 family member, is correlated with worse survival in lung adenocarcinomas. Here, we show that BCL-B can mitigate cell death initiation through interaction the effector protein BOK. We found this promote sublethal mitochondrial outer membrane permeabilization (MOMP) and consequently generate apoptosis-flatliners, which represent a source drug-tolerant persister cells (DTPs). The engagement endothelial-mesenchymal-transition (EMT) further promotes...
In patients with metastatic non-small cell lung cancer (NSCLC) high programmed death-ligand 1 (PD-L1) expression, there is still a lack of biomarkers to identify maximum benefit from first-line treatment checkpoint inhibitor therapy (CIT) alone. This work examines the impact different ABO blood groups (BG) on response CIT monotherapy. Retrospective analysis stage IV NSCLC and PD-L1 expression (tumor proportional score/TPS ≥ 50%), receiving pembrolizumab alone or in combination chemotherapy...
Abstract Immune-mediated effector molecules can limit cancer growth, but lack of sustained immune activation in the tumour microenvironment restricts antitumour immunity. New therapeutic approaches that induce a strong and prolonged would represent major immunotherapeutic advance. Here we show arenaviruses lymphocytic choriomeningitis virus (LCMV) clinically used Junin vaccine (Candid#1) preferentially replicate cells variety murine human models. Viral replication leads to local activation,...
Background/Aims: Unexpected transmissions of viral pathogens during solid organ transplantation (SOT) can result in severe, life-threatening diseases transplant recipients. Immune activation contributes to disease onset. However mechanisms balancing the immune response against transmitted infection through remain unknown. Methods & Results: Here we found, using lymphocytic choriomeningitis virus (LCMV), that LCMV infected hearts led exhaustion specific CD8+ T cells, persistence organs...
Graft versus host disease (GvHD) occurs in 20% of cases with patients having an MHC I matched bone marrow transplantation (BMT). Mechanisms causing this remain to be studied.Here we used a CD8+ T cell transgenic mouse line (P14/CD45.1+) and DEE mice bearing ubiquitously the glycoprotein 33-41 (GP33) antigen derived from major lymphocytic choriomeningitis virus (LCMV) epitope study mechanisms tolerance anti-host reactive cells after BMT.We found that (P14 cells) were not negatively selected...
Hoerning A, Kalkavan H, Rehme C, Menke J, Worm K, Garritsen HSP, Büscher R, Hoyer PF. Quantitative real‐time ARMS‐qPCR for mitochondrial DNA enables accurate detection of microchimerism in renal transplant recipients. Pediatr Transplantation 2011: 15: 809–818. © 2011 John Wiley & Sons A/S. Abstract: The presence peripheral blood solid organ recipients has been postulated to be beneficial allograft acceptance. Kinetics donor cell trafficking and accumulation pediatric are largely unknown....
Abstract Early detection of tumor activity in clinically asymptomatic patients has the potential to improve quality life and prevent unnecessary exposure toxic therapies. DNA methylation is one most studied, stable, fundamental epigenetic marks represents a prominent alteration cancers. Analysis methylation, particularly liquid biopsies been introduced cancer diagnosis risk stratification. Despite indisputable achievements, translation into clinical practice lagging behind, primarily due 1)...
Approximately every second patient with uveal melanoma develops distant metastases, the liver as predominant target organ. While median survival after diagnosis of metastases is limited to a year, yet-to-be-defined subgroups patients experience more favorable outcome. Therefore, prognostic biomarkers could help identify distinct risk groups guide counseling, therapeutic decision-making, and stratification study populations. To this end, we retrospectively analyzed cohort 101 newly diagnosed...
Abstract With the integration of PD-1 and CTLA-4 targeting immune checkpoint blockade into cancer treatment regimes, anti-tumoral cytotoxicity tumor-specific CD8 + T cells is well established. However, while unresponsiveness against big tumors mainly explained by cell exhaustion, other factors contributing to failure remain not studied. Here we used a mouse melanoma model study interaction growing tumor cells, innate immunity responses induced viral replication. Mouse (B16F10-OVA) infections...
Abstract DNA methylation is an extensively studied, stable, and fundamental epigenetic alteration in most cancer types 1 . Single-base-pair resolution analyses of currently feasible 2 Analysis methylation, liquid biopsies hold practice-changing potentials 3-6 Despite undeniable progress, clinical translation lags behind, mainly due to: 1) Challenges associated with analysis. 2) Fragmentation circulating cell-free (ccfDNA), worsened by bisulfite treatment. 3) Lack validation for reported...
2086 Background: Deregulation of the PI3K/AKT pathway has been preclinically involved in pathophysiology GBM. The mammalian target rapamycin (mTOR) is an important downstream mediator signalling. mTOR-inhibitor temsirolimus (Tem) achieves significant drug levels brain. Thus, Tem may be effectively combined with irinotecan (Iri) which shown promising results combination bevacizumab patients (pts) reGBM refractory to temozolomide (Tmz) phase II. Exposure as well Iri substantially reduced pts...