- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- CAR-T cell therapy research
- interferon and immune responses
- Glioma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Angiogenesis and VEGF in Cancer
- Cytokine Signaling Pathways and Interactions
- Single-cell and spatial transcriptomics
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Lymphatic System and Diseases
- Melanoma and MAPK Pathways
- T-cell and B-cell Immunology
- Phagocytosis and Immune Regulation
- Advanced Electron Microscopy Techniques and Applications
- Nanoplatforms for cancer theranostics
- Cancer Research and Treatments
- Cell Image Analysis Techniques
- Cancer, Stress, Anesthesia, and Immune Response
- Medical Imaging Techniques and Applications
- Photoacoustic and Ultrasonic Imaging
- Cancer Cells and Metastasis
- Mathematical Biology Tumor Growth
Heidelberg University
2022-2025
University Hospital Heidelberg
2022-2025
German Cancer Research Center
2022-2025
Deutschen Konsortium für Translationale Krebsforschung
2024
Gentofte Hospital
2024
University Medical Centre Mannheim
2022-2023
Bernstein Center for Computational Neuroscience Heidelberg-Mannheim
2023
Karolinska Institutet
2022-2023
Heidelberg University
2022
Science for Life Laboratory
2022
Abstract Glioblastoma, the most common and aggressive primary brain tumor type, is considered an immunologically “cold” with sparse infiltration by adaptive immune cells. Immunosuppressive tumor-associated myeloid cells are drivers of progression. Therefore, targeting reprogramming intratumoral appealing therapeutic strategy. Here, we investigate a β-cyclodextrin nanoparticle (CDNP) formulation encapsulating Toll-like receptor 7 8 (TLR7/8) agonist R848 (CDNP-R848) to reprogram in glioma...
Murine syngeneic tumor models have been used extensively for cancer research several decades and instrumental in driving the discovery development of immunotherapies. These are very simplistic models, but recent reports have, however, indicated that different inoculated cell lines can lead to formation unique microenvironments (TMEs). To gain more knowledge from studies based on it is essential obtain an in-depth understanding cellular molecular composition TME models. Additionally, other...
Abstract T cell receptor-engineered cells (TCR-T) could be advantageous in glioblastoma by allowing safe and ubiquitous targeting of the glioblastoma-derived peptidome. Protein tyrosine phosphatase receptor type Z1 (PTPRZ1), is a clinically targetable antigen associated with stemness. Here, we identify therapeutic HLA-A*02-restricted PTPRZ1-reactive TCR retrieved from vaccinated patient. Single-cell sequencing primary brain tumors shows PTPRZ1 overexpression malignant cells, especially stem...
<p>Supplementary Figure S3 shows characterization of intracranial tumor microenvironment and macrophages after IFN-beta exposure.</p>
<p>Supplementary Figure S1 characterizes modified cell lines, showing transduction vectors, confirmatory flow cytometry of protein induction, and in vitro proliferation.</p>
<p>Supplementary Figure S2 depicts flow cytometry gating strategies for all assays.</p>
<p>Supplementary Figure S4 shows type I IFN response signature gene expression in human melanoma brain metastasis macrophages.</p>
Rationale: Intrinsic brain tumors, such as gliomas are largely resistant to immunotherapies including immune checkpoint blockade. Adoptive cell therapies (ACT) chimeric antigen receptor (CAR) or T (TCR)-transgenic therapy targeting glioma-associated antigens an emerging field in glioma immunotherapy. However, imaging techniques for non-invasive monitoring of adoptively transferred cells homing the microenvironment currently lacking. Methods: Ultrasmall iron oxide nanoparticles (NP) can be...
The expression of pro-lymphangiogenic VEGF-C in primary tumors is associated with sentinel lymph node metastasis most solid cancer types. However, the impact on distant organ remains unclear. Perivascular tumor-associated macrophages (TAMs) play a crucial role guiding hematogenous spread cells by establishing metastatic pathways within tumor microenvironment. This process supports breast cell intravasation and dissemination. We show here that VEGF-C-expressing TAMs reduce dissemination...
Abstract Glioblastoma is the most common and aggressive primary malignant brain tumor with poor prognosis. Novel immunotherapeutic approaches are currently under investigation. Even though magnetic resonance imaging (MRI) important tool for treatment monitoring, response assessment often hampered by therapy-related tissue changes. As therapy-associated reactions differ structurally, we hypothesize that biomechanics could be a pertinent proxy differentiation. Longitudinal MRI elastography...
Glioblastoma is the most common malignant primary brain tumor with poor overall survival. Magnetic resonance imaging (MRI) main modality for glioblastoma but has inherent shortcomings. The molecular and cellular basis of MR signals incompletely understood. We established a ground truth-based image analysis platform to coregister MRI light sheet microscopy (LSM) data each other an anatomic reference atlas quantification 20 predefined subregions. Our pipeline also includes segmentation...
<title>Abstract</title> Response to CAR-T cell therapy in glioblastoma (GB) patients is limited, particularly because of the paucity surface immunotherapeutic targets or low antigen sensitivity. Moreover, tonic CAR signaling leads T dysfunction eventually resulting non-durable responses. receptor-engineered (TCR-T) circumvents latter limitation by allowing safe and ubiquitous targeting GB-derived peptidome. Protein tyrosine phosphatase receptor type Z1 (PTPRZ1), a GB associated with...
MRI and MRE were used to monitor the effects of immunotherapy on tumor volume, FA biomechanics murine orthotopic glioma. Treated tumors significantly smaller, softer had lower than controls. This difference was most pronounced when comparing stiffness both groups. Controls revealed heterogeneous stiffness. We hypothesize that this is caused by viable cells alternated with necrotic areas presumably immune-suppressive iba1-positive cells. In contrast, biomechanical properties treated animals...
Abstract BACKGROUND Type I interferons (IFN) such as IFNβ are pro-inflammatory cytokines involved in antiviral immune responses. Increasing evidence indicates that the success of several anticancer therapies, including radiotherapy, relies on immune-stimulatory effects type IFNs innate and adaptive cells tumor microenvironment (TME). Tumor-associated macrophages (TAMs) one most abundant TME melanoma brain metastases (MBMs) can exert potent immune-suppressive functions compromising effective...
Abstract Despite the remarkable success of chimeric antigen receptor (CAR)-T cell treatment for patients with hematologic malignancies, this method has yet failed to confer meaningful survival benefits suffering from glioblastoma (GB), most lethal type brain tumor. This highlights need develop novel CAR-T approaches disease. CD70 is a member tumor necrosis factor (TNFR) superfamily. Although absent on normal tissue, it ectopically expressed in substantial fraction GB patients, indicating its...
Type I interferons (IFN) are immune-stimulatory cytokines involved in antiviral and antitumor immune responses. They enhance the efficacy of immunogenic anticancer therapies such as radiotherapy by activating both innate adaptive cells. Macrophages one most abundant cells microenvironment melanoma brain metastases (MBM) can exert potent immune-suppressive functions. Here, we investigate potential tumoral type IFNs to repolarize tumor-associated macrophages (TAM) two murine MBM models assess...
<div>Abstract<p>Type I interferons (IFN) are immune-stimulatory cytokines involved in antiviral and antitumor immune responses. They enhance the efficacy of immunogenic anticancer therapies such as radiotherapy by activating both innate adaptive cells. Macrophages one most abundant cells microenvironment melanoma brain metastases (MBM) can exert potent immune-suppressive functions. Here, we investigate potential tumoral type IFNs to repolarize tumor-associated macrophages (TAM)...
<div>Abstract<p>Type I interferons (IFN) are immune-stimulatory cytokines involved in antiviral and antitumor immune responses. They enhance the efficacy of immunogenic anticancer therapies such as radiotherapy by activating both innate adaptive cells. Macrophages one most abundant cells microenvironment melanoma brain metastases (MBM) can exert potent immune-suppressive functions. Here, we investigate potential tumoral type IFNs to repolarize tumor-associated macrophages (TAM)...