A5083188874- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- Radiomics and Machine Learning in Medical Imaging
- Advanced Biosensing Techniques and Applications
- Immune cells in cancer
- Colorectal Cancer Treatments and Studies
- Cutaneous Melanoma Detection and Management
- Neuroinflammation and Neurodegeneration Mechanisms
- Single-cell and spatial transcriptomics
- Medical Imaging Techniques and Applications
- Glioma Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Melanoma and MAPK Pathways
- Computational Drug Discovery Methods
- S100 Proteins and Annexins
- Long-Term Effects of COVID-19
- Advanced X-ray and CT Imaging
- Ferroptosis and cancer prognosis
- Antimicrobial Peptides and Activities
- Cancer-related gene regulation
- Protein Degradation and Inhibitors
- MicroRNA in disease regulation
- Chemokine receptors and signaling
Newcastle University
2025
University of Basel
2022-2024
University Hospital of Basel
2022-2024
Freiwillige Akademische Gesellschaft
2023
University Hospital of Zurich
2016-2023
University of Zurich
2016-2023
SIB Swiss Institute of Bioinformatics
2023
Roche Pharma AG (Germany)
2023
Roche (Switzerland)
2023
Freie Universität Berlin
2012
Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including imaging data corresponding multidimensional characterization immune mediators cerebrospinal fluid (CSF) plasma patients belonging to different Neuro-COVID severity classes. The...
Glioblastoma (GBM) is the most aggressive form of primary brain tumor, for which effective therapies are urgently needed. Cancer cells capable evading clearance by phagocytes such as microglia- and monocyte-derived through engaging tolerogenic programs. Here, we found that high expression sialic acid–binding immunoglobulin-like lectin 9 (Siglec-9) correlates with reduced survival in patients GBM. Using cell-specific knockouts Siglec-E, murine functional homolog Siglec-9, together single-cell...
Abstract Many metastatic melanoma patients experience durable responses to anti-PD1 and/or anti-CTLA4; however, a significant proportion (over 50%) do not benefit from the therapies. In this study, we sought assess pretreatment liquid biopsies for biomarkers that may correlate with response checkpoint blockade. We measured combinatorial diversity evenness of T-cell receptor (TCR) repertoire (the DE50, low values corresponding more clonality and lack TCR diversity) in peripheral blood...
We assessed the predictive potential of positron emission tomography (PET)/CT-based radiomics, lesion volume, and routine blood markers for early differentiation pseudoprogression from true progression at 3 months.112 patients with metastatic melanoma treated immune checkpoint inhibition were included in our study. Median follow-up duration was 22 months. 716 metastases segmented individually on CT 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET imaging three timepoints: baseline (TP0), months...
A patient-tailored, ex vivo drug response platform for glioblastoma (GBM) would facilitate therapy planning, provide insights into treatment-induced mechanisms in the immune tumor microenvironment (iTME), and enable discovery of biomarkers response. We cultured regionally annotated GBM explants perfusion bioreactors to assess iTME responses immunotherapy. Explants were treated with anti-CD47, anti–PD-1, or their combination, analyzed by multiplexed microscopy [CO-Detection indEXing (CODEX)],...
A role of WNT signaling for primary breast cancers the basal-like subtype and as a predictor brain metastasis has been described. However, responsible ligand not identified. To further clarify this question, we comparatively investigated 22 human cancer metastases well highly invasive cell line MDA-MB-231 weakly motile MCF-7 models luminal subtype. WNT5A B were found overexpressed in cells compared with MCF-7. This corresponded to reduction invasiveness by inhibitors, whereas invasion was...
Abstract The immune response to melanoma improves the survival in untreated patients and predicts checkpoint blockade. Here, we report genetic environmental predictors of a large primary cutaneous cohort. Bioinformatic analysis 703 tumor transcriptomes was used infer cell infiltration categorize tumors into subgroups, which were then investigated for association with biological pathways, clinicopathologic factors, copy number alterations. Three “low”, “intermediate”, “high” signals,...
Abstract Purpose: Despite high clinical need, there are no biomarkers that accurately predict the response of patients with metastatic melanoma to anti-PD-1 therapy. Experimental Design: In this multicenter study, we applied protein depletion and enrichment methods prior various proteomic techniques analyze a serum discovery cohort (n = 56) three independent validation cohorts 80, n 12, 17). Further analyses by literature survival analysis followed. Results: We identified several...
The t-haplotype, a variant form of the t-complex region on mouse chromosome 17, acts as selfish genetic element and is transmitted at high frequencies (> 95%) from heterozygous (t/+) males to their offspring. This phenotype termed transmission ratio distortion (TRD) caused by interaction responder (Tcr) with several quantitative trait loci (QTL), distorters (Tcd1 Tcd4), all located within t-haplotype region. Current data suggest that collectively impair motility sperm derived t/+ males;...
Abstract Immunotherapy profoundly impacted cancer treatments by harnessing the patient’s immune system. Phagocytosis, process whereby cells engulf and destroy foreign particles or cells, plays a critical role in tumour cell clearance. Herein, we introduce novel concept termed “ENPHASYS” – En hancement of Pha gocytic Sy napse s designed to direct amplify phagocytosis using heterobifunctional molecules named phagocytic synapse enhancers (PSEs). By engineering de novo PD-L1 binder linked...
Abstract Aim: There has been renewed interest in pursuing cyclin-dependent kinase 2 (CDK2) as a therapeutic target for cancer treatment, given its essential role driving the survival of CCNE1-amplified tumors and mediating resistance to CDK4/6 inhibitor treatment estrogen receptor positive breast cancer. This resulted identification next generation orthosteric inhibitors which have increased selectivity CDK2 versus other CDK-family members. study aimed contrast genetic chemical perturbation...
A significant challenge for chimeric antigen receptor (CAR) T cell therapy against glioblastoma (GBM) is its immunosuppressive microenvironment, which densely populated by protumoral glioma-associated microglia and macrophages (GAMs). Myeloid immune checkpoint targeting the CD47-signal regulatory protein alpha (SIRPα) axis induces GAM phagocytic function, but CD47 blockade monotherapy associated with toxicity low bioavailability in solid tumors. In this work, we engineer a CAR epidermal...
Glioblastoma (GBM) harbors a highly immunosuppressive tumor microenvironment (TME) which influences glioma growth. Major efforts have been undertaken to describe the TME on single-cell level. However, human data regional differences within remain scarce. Here, we performed high-depth RNA sequencing (scRNAseq) paired biopsies from center, peripheral infiltration zone and blood of five primary GBM patients. Through analysis >45,000 cells, revealed regionally distinct transcription profile...
Glioblastoma (GBM) harbors a highly immunosuppressive tumor microenvironment (TME) which influences glioma growth. Major efforts have been undertaken to describe the TME on single-cell level. However, human data regional differences within remain scarce. Here, we performed high-depth RNA sequencing (scRNAseq) paired biopsies from center, peripheral infiltration zone and blood of five primary GBM patients. Through analysis >45,000 cells, revealed regionally distinct transcription profile...
Background Many cancer patients do not obtain clinical benefit from immune checkpoint inhibition. Checkpoint blockade targets T cells, suggesting that tyrosine kinase activity profiling of baseline peripheral blood mononuclear cells may predict outcome. Methods Here a total 160 with advanced melanoma or non-small-cell lung (NSCLC), treated anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) anti-programmed cell death 1 (anti-PD-1), were divided into five discovery and...
We explored imaging and blood bio-markers for survival prediction in a cohort of patients with metastatic melanoma treated immune checkpoint inhibition.94 consecutive inhibition were included into this study. PET/CT was available at baseline (Tp0), 3 months (Tp1) 6 (Tp2) after start immunotherapy. Radiological response Tp2 evaluated using iRECIST. Total tumor burden (TB) each time-point measured relative change TB compared to calculated. LDH, CRP S-100B also analyzed. Cox proportional...
3026 Background: Anti-PD-1 and/or anti-CTLA-4 antibodies show durable responses in metastatic melanoma. Measuring the diversity of T lymphocytes pre-treatment liquid biopsies may help stratify patients for immunotherapy. Methods: In this retrospective blinded study, we used a multi-N-plex polymerase chain reaction (PCR) assay to measure TCR combinatorial from genomic DNA peripheral blood melanoma treated with (n = 40) or anti-PD-1 36). A receiver operating characteristic (ROC) curve was...