A5062772363- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- vaccines and immunoinformatics approaches
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Gene expression and cancer classification
- Cell Adhesion Molecules Research
- Glycosylation and Glycoproteins Research
- Glioma Diagnosis and Treatment
- Chemokine receptors and signaling
- T-cell and B-cell Immunology
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Immune cells in cancer
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Toxin Mechanisms and Immunotoxins
- Dermatology and Skin Diseases
- Radiomics and Machine Learning in Medical Imaging
- Fungal and yeast genetics research
- Hair Growth and Disorders
University of Zurich
2017-2025
ETH Zurich
2021-2025
Ludwig-Maximilians-Universität München
2013-2014
Center for Integrated Protein Science Munich
2014
Intratumoral immune cells are crucial for tumor control and antitumor responses during immunotherapy. Immune cell trafficking into tumors is mediated by binding of specific receptors to chemokines, a class secreted chemotactic cytokines. To broadly characterize chemokine expression function in melanoma, we used multiplexed mass cytometry-based imaging protein markers RNA transcripts analyze the landscape infiltration metastatic melanoma samples. Tumors that lacked were devoid most profiled...
Multiplexed imaging is increasingly used to study tissue architecture in health and disease. To investigate the cancer tumor microenvironment, typically either micro-arrays or small patient cohorts are collect process data. However, studies performed over course of years, collecting data from thousands samples rare require specialized workflows ensure sample throughput reproducibility for production processing. Here, we present two such multiplexed immunofluorescence mass cytometry tissues...
RNA polymerase II (Pol II) is the central enzyme that carries out eukaryotic mRNA transcription and consists of a 10-subunit catalytic core subcomplex subunits Rpb4 Rpb7 (Rpb4/7). Rpb4/7 has been proposed to dissociate from Pol II, enter cytoplasm, function there in translation degradation. Here we provide evidence mainly functions nuclear synthesis by as well arguing against an important cytoplasmic role We used metabolic labeling comparative Dynamic Transcriptome Analysis show deletion...
Epidermal growth factor receptor (EGFR)-targeted anticancer therapy induces stigmatizing skin toxicities affecting patients' quality of life and adherence. The lack mechanistic details underlying these adverse events hampers their management. We found that EGFR/ERK signaling is required in LRIG1-positive stem cells during de novo hair eruption to secure barrier integrity prevent the invasion commensal microbiota inflammatory disease. EGFR-deficient epidermis permissive for outgrowth displays...
Abstract Recent advances in multiplexed imaging methods allow simultaneous detection of dozens proteins and hundreds RNAs, enabling deep spatial characterization both healthy diseased tissues. Parameters for the design optimal multiplex studies, especially those estimating how much area has to be imaged capture all cell phenotype clusters, are lacking. Here, using a transcriptomic atlas tumor human tissues, we developed statistical framework that determines number fields view necessary...
Abstract Purpose: The low mutational load of some cancers is considered one reason for the difficulty to develop effective tumor vaccines. To overcome this problem, we developed a strategy design neopeptides through single amino acid mutations enhance their immunogenicity. Experimental Design: Exome and RNA sequencing as well in silico HLA-binding predictions autologous HLA molecules were used identify candidate neopeptides. Subsequently, HLA-anchor placements deduce putative T-cell receptor...
Abstract Intratumoral immune cells are crucial for tumor control and anti-tumor responses during immunotherapy. Immune cell trafficking into tumors is mediated by chemokines, which expressed secreted upon various stimuli interact with specific receptors. To broadly characterize chemokine expression function in tumors, we have used multiplex mass cytometry-based imaging of protein markers RNA transcripts to analyze the landscape infiltration metastatic melanoma samples. Tumors that lacked...
Abstract Recent advances in multiplexed imaging methods allow simultaneous detection of dozens proteins and hundreds RNAs enabling deep spatial characterization both healthy diseased tissues. Parameters for design optimal sequencing-based experiments have been established, but such parameters, especially those estimating how much area has to be imaged capture all cell phenotype clusters, are lacking multiplex studies. Here, using a transcriptomic atlas tumor human tissues, we developed new...
Single-cell, spatially resolved 9omics analysis of tissues is poised to transform biomedical research and clinical practice. We have developed a computational histology topography cytometry toolbox (histoCAT) enable the interactive, quantitative, comprehensive exploration phenotypes individual cells, cell-to-cell interactions, microenvironments, morphological structures within intact tissues. histoCAT will be useful in all areas tissue-based research. highlight unique abilities by highly...
<p>Designed mutations increase the stimulatory strength of D-neopeptides above N-peptides. (A) TILs were stimulated with 5 μM class I-peptides, including N-peptides and D-neopeptides, for days. replicate wells tested proliferation, proliferation was measured by 3H-thymidine incorporation assay. In each group, their corresponding are included, designed mutated positions highlighted in red box. The blue dotted line indicates mean value no peptide control. plus three standard deviations...
<p>Over-/highly expressed genes in the primary glioblastoma when compared with cohort TCGA Database.</p>
<p>Predicted TSA/TAA-derived N-peptides and D-neopeptides</p>
<p>Peripheral blood T cell responses to v-peptides increase with repetitive vaccination. (A) PBMCs were collected 3 weeks after the 2nd peptide cocktail vaccination, and CD45RA-negative stimulated 4 μg/mL Tetanus toxoid, 2 μM CEF II pool or 5 for 7 days. 5-10 replicate wells tested proliferation, proliferation measured by 3H-thymidine incorporation assay. before vaccination used as reference. The strength is depicted stimulation index (SI). red dotted line indicates a stimulatory...
<p>PBMCs collected before vaccination show low/no response to candidate vaccine peptides. (A) The nomenclature of the N-peptides and D-neopeptides. I or II indicate if peptides were chosen/designed for HLA class -II binding; MUT/RNA/GBM indicates a naturally mutated peptide (MUT), derivation from over-/highly expressed genes (RNA) known glioblastoma (GBM) targets; X number peptide; 0 1 had been artificially (1) not (0); (’) that contained amino acid. (B) PBMCs stimulated with 4 μg/mL...
<p>Vaccinated D-neopeptides activate tumor-infiltrating antitumor T cells. (A) Circos plots provide an overview of the frequencies Vβ-Jβ pairing in primary and recurrent tumors. (B) Surface TCR β chain expression D-neopeptide-specific CD4+ TCCs was analyzed using FACs.</p>
<p>Increased T lymphocyte infiltration in the recurrent compared to primary tumor. (A) CD3 immunohistochemical staining and (B) Three fields of view were selected counted CD3+ cells both perivascular peritumoral areas tumors using ImageJ. Scale bars are indicated figures.</p>
<p>TILs do not respond to N-class I-peptides. TILs were stimulated with 5- or 10 μM I-peptides for 5 days. replicate wells tested proliferation, and proliferation was measured by 3H-thymidine incorporation assay. The strength is depicted as SI. (#) indicates the peptide that used in 1st 4th vaccinations. Data are expressed mean ± SEM.</p>
<p>Activated T lymphocytes in recurrent tumor interact with macrophages. (A) Expression of cell activating markers HLA-DR and Tim-3 the perivascular areas peritumoral primary was detected by IMC. (B) CD3-CD7+ NK cells infiltrated (C) Pro-inflammatory CD11c+ CD68+ macrophages, which had tumor, were (D) Colocalization analysis macrophages CD3+ Scale bars are indicated figures.</p>
<p>Schematic outline of the personalized peptide vaccination. (A) Timeline clinical events for a patient with glioblastoma in whom we applied highly I. Vaccine design. Surgically resected primary and PBMCs were collected. Somatic mutants over-/highly expressed genes identified as TSAs TAAs by WES RNA-seq, HLA genotype DNA sequencing. Potential vaccine peptides predicted selected from based on binding prediction. Peptide cocktails containing ~25 class I or II molecules prepared II....
<p>Activated T lymphocytes in recurrent tumor interact with macrophages. (A) Expression of cell activating markers HLA-DR and Tim-3 the perivascular areas peritumoral primary was detected by IMC. (B) CD3-CD7+ NK cells infiltrated (C) Pro-inflammatory CD11c+ CD68+ macrophages, which had tumor, were (D) Colocalization analysis macrophages CD3+ Scale bars are indicated figures.</p>
<p>Increased T lymphocyte infiltration in the recurrent compared to primary tumor. (A) CD3 immunohistochemical staining and (B) Three fields of view were selected counted CD3+ cells both perivascular peritumoral areas tumors using ImageJ. Scale bars are indicated figures.</p>