A5010344388- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Cancer Mechanisms and Therapy
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Glioma Diagnosis and Treatment
- Cancer Cells and Metastasis
- 3D Printing in Biomedical Research
- Immune cells in cancer
- PARP inhibition in cancer therapy
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
- MicroRNA in disease regulation
- Multiple Myeloma Research and Treatments
- Radiopharmaceutical Chemistry and Applications
- Cancer, Hypoxia, and Metabolism
- Histone Deacetylase Inhibitors Research
- NF-κB Signaling Pathways
- Genomics, phytochemicals, and oxidative stress
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
Leibniz Institute for Immunotherapy
2022-2024
University of Regensburg
2024
Leibniz Association
2022-2024
University Hospital Regensburg
2019-2021
•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...
Radiotherapy is a mainstay cancer therapy whose antitumor effects partially depend on T cell responses. However, the role of Natural Killer (NK) cells in radiotherapy remains unclear. Here, using reverse translational approach, we show central NK radiation-induced immune response involving CXCL8/IL-8–dependent mechanism. In randomized controlled pancreatic trial, CXCL8 increased under radiotherapy, and positively correlated with prolonged overall survival. Accordingly, preferentially...
CD8 T lymphocytes are classically viewed as cytotoxic cells. Whether human cells can, in parallel, induce a tissue regeneration program is poorly understood. Here, antigen-specific assay systems revealed that not only mediated cytotoxicity but also promoted remodeling. Activated could produce the epidermal growth factor receptor (EGFR)-ligand amphiregulin (AREG) and sensitize epithelial for enhanced potential. Blocking EGFR or effector cytokines IFN-γ TNF inhibit This regenerative tumor...
Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a surface receptor, is expressed on normal epithelial tissue and highly in cancers of high unmet medical need, such as non-small lung, pancreatic, colorectal cancer. CEACAM receptors undergo homo- heterophilic interactions thereby regulating homeostasis angiogenesis, cancer, tumor invasion metastasis. CEACAM6 expression malignant plasma cells inhibits antitumor activity T cells, we hypothesize similar function cancer cells....
At present, targeting PD-1/PD-L1 axis for immune checkpoint inhibition has improved treatment of various tumor entities, including head and neck squamous cell carcinoma (HNSCC). However, one part the patient cohort still shows little improvement or even hyperprogression. We established three radioresistant (RR) radiosensitive (RS) HNSCC lines. RR cells showed prolonged survival as well delayed diminished apoptosis after irradiation with vimentin expression but no E-cadherin expression,...
Abstract Glioblastoma (GB) IDH-wildtype is the most malignant primary brain tumor. It particularly resistant to current immunotherapies. Translocator protein 18 kDa (TSPO) upregulated in GB and correlates with malignancy poor prognosis, but also increased immune infiltration. Here, we studied role of TSPO regulation resistance human cells. The tumor was experimentally determined initiating cells (BTICs) cell lines through genetic manipulation expression subsequent cocultures antigen specific...
Abstract TSPO is a promising novel tracer target for positron-emission tomography (PET) imaging of brain tumors. However, due to the heterogeneity cell populations that contribute TSPO-PET signal, interpretation may be challenging. We therefore evaluated enrichment/expression in connection with its underlying histopathological and molecular features gliomas. analyzed expression regulatory mechanisms large silico datasets by performing direct bisulfite sequencing promotor. In glioblastoma...
The success of cancer immunotherapy is limited by resistance to immune checkpoint blockade. We therefore conducted a genetic screen identify genes that mediated against CTLs in anti-PD-L1 treatment-refractory human tumors. Using PD-L1-positive multiple myeloma cells cocultured with tumor-reactive bone marrow-infiltrating CTL as model, we identified calcium/calmodulin-dependent protein kinase 1D (CAMK1D) key modulator tumor-intrinsic resistance. CAMK1D was coexpressed PD-L1 anti-PD-L1/PD-1...
Background Cancer immunotherapeutic strategies showed unprecedented results in the clinic. However, many patients do not respond to immuno-oncological treatments due occurrence of a plethora immunological obstacles, including tumor intrinsic mechanisms resistance cytotoxic T-cell (TC) attack. Thus, deeper understanding these is needed develop successful immunotherapies. Methods To identify novel genes that protect cells from effective TC-mediated cytotoxicity, we performed genetic screening...
Conventional 2D cultures are commonly used in cancer research though they come with limitations such as the lack of microenvironment or reduced cell heterogeneity. In this study, we investigated what respect a scaffold-based (Matrigel™) 3D culture technique can ameliorate cultures. NGS-based bulk and single-cell sequencing matched pairs models showed an altered transcription key immune regulatory genes around 36% models, indicating reoccurrence suppressive phenotype. Changes included...
Abstract Immunotherapy by blockade of the PD-1/PD-L1 checkpoint demonstrated amazing tumor response in advanced cancer patients including head and neck squamous cell carcinoma (HNSCC). However, majority HNSCC still show little improvement or even hyperprogression. Irradiation is currently investigated as synergistic treatment modality to immunotherapy it increases number T-cells thereby enhancing efficacy immunotherapy. Apart from this immunogenic context a growing amount data indicates that...
<div>Abstract<p>The success of cancer immunotherapy is limited by resistance to immune checkpoint blockade. We therefore conducted a genetic screen identify genes that mediated against CTLs in anti–PD-L1 treatment–refractory human tumors. Using PD-L1–positive multiple myeloma cells cocultured with tumor-reactive bone marrow–infiltrating CTL as model, we identified calcium/calmodulin-dependent protein kinase 1D (CAMK1D) key modulator tumor-intrinsic resistance. CAMK1D was...
<div>Abstract<p>The success of cancer immunotherapy is limited by resistance to immune checkpoint blockade. We therefore conducted a genetic screen identify genes that mediated against CTLs in anti–PD-L1 treatment–refractory human tumors. Using PD-L1–positive multiple myeloma cells cocultured with tumor-reactive bone marrow–infiltrating CTL as model, we identified calcium/calmodulin-dependent protein kinase 1D (CAMK1D) key modulator tumor-intrinsic resistance. CAMK1D was...
<p>Supplementary Figures 1-7</p>
<p>Supplementary Figures 1-7</p>
Abstract 3D (organoid) models in cancer research are considered the novel gold standard for vitro experiments. Nevertheless, a variety of different protocols exits and often used uncritically lack further validation. In this study, we aimed to characterize scaffold-based (MatrigelTM) glioma cell culture approach. We compared technique conventional 2D culturing its efficacy generating respect exact modeling properties. Models were generated from 62 patients with CNS tumors, most them...