Sandra Tietscher
A5073045394- Cancer Immunotherapy and Biomarkers
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- Melanoma and MAPK Pathways
- Radiopharmaceutical Chemistry and Applications
- Immune cells in cancer
- Cancer Cells and Metastasis
- Cell Image Analysis Techniques
- Advanced Proteomics Techniques and Applications
- CRISPR and Genetic Engineering
- Breast Cancer Treatment Studies
- Brain Metastases and Treatment
- Medical Imaging Techniques and Applications
- Marketing and Advertising Strategies
- Evolution and Genetic Dynamics
- Polish socio-economic development
- Management and Organizational Practices
- Escherichia coli research studies
- RNA and protein synthesis mechanisms
- Ferroptosis and cancer prognosis
- Advanced Fluorescence Microscopy Techniques
- HER2/EGFR in Cancer Research
- Cancer, Stress, Anesthesia, and Immune Response
- Antibiotic Resistance in Bacteria
University of Zurich
2020-2024
ETH Zurich
2021-2022
Life Science Zurich
2021-2022
IIT@MIT
2021
McGovern Institute for Brain Research
2021
Engineering Arts (United States)
2021
Allen Institute
2021
Howard Hughes Medical Institute
2021
Uppsala University
2018
Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, open source computational methods. Using we generated resource 51,926 matched cell images diverse types including lines, xenografts, diagnostic samples with limited...
Abstract A holistic understanding of tissue and organ structure function requires the detection molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous up to 40 antigens transcripts using metal-tagged antibodies but has so far been restricted two-dimensional imaging. Here we report development 3D IMC for multiplexed analysis at single-cell resolution demonstrate utility technology by human breast cancer samples. The resulting...
Cancer-associated fibroblasts (CAFs) are a diverse cell population within the tumour microenvironment, where they have critical effects on evolution and patient prognosis. To define CAF phenotypes, we analyse single-cell RNA sequencing (scRNA-seq) dataset of over 16,000 stromal cells from tumours 14 breast cancer patients, based which functionally annotate nine phenotypes one class pericytes. We validate this classification system in four additional types use highly multiplexed imaging mass...
Abstract Immune checkpoint therapy in breast cancer remains restricted to triple negative patients, and long-term clinical benefit is rare. The primary aim of immune blockade prevent or reverse exhausted T cell states, but exhaustion tumors not well understood. Here, we use single-cell transcriptomics combined with imaging mass cytometry systematically study environments human that either do contain cells, a focus on luminal subtypes. We find the presence PD-1 high exhaustion-like phenotype...
How cell-to-cell copy number alterations that underpin genomic instability
Coral reefs are colored by eukaryotic chromoproteins (CPs) that homologous to green fluorescent protein. CPs differ from proteins (FPs) intensely absorbing visible light give strong colors in ambient light. This endows with certain advantages over FPs, such as instrument-free detection uncomplicated ultra-violet damage or background fluorescence, efficient Förster resonance energy transfer (FRET) quenching, and photoacoustic imaging. Thus, have found utility genetic markers teaching,...
The heterogeneity of breast cancer plays a major role in drug response and resistance has been extensively characterized at the genomic level. Here, single-cell mass cytometry (BCMC) panel is optimized to identify cell phenotypes their oncogenic signalling states biobank patient-derived tumour xenograft (PDTX) models representing diversity human cancer. BCMC identifies 13 cellular (11 2 murine), associated with both subtypes specific features. Pre-treatment phenotypic composition determinant...
Abstract Breast cancer is the most commonly diagnosed in women, with distant metastasis being main cause of breast cancer-related deaths. Elucidating changes tumor and immune ecosystems that are associated metastatic disease essential to improve understanding ultimately treatment metastasis. Here, we developed an in-depth, spatially resolved single-cell atlas phenotypic diversity cells primary human tumors matched metastases, using imaging mass cytometry analyze a total 75 unique antibody...
<p>Immune cell phenotypes in PT and metastases. <b>A,</b> Uniform Manifold Approximation Projection for Dimension Reduction (UMAP) visualization of all lymphoid cells from the T-cell panel dataset, colored by type (<i>n</i> = 87 patients). <b>B,</b> Heatmap showing mean expression T-cell–relevant markers across different phenotypic subtypes after graph-based clustering patients; <i>n</i>_cells 91,000). Euclidean distance with average...
<p>Overview of the clinical cohort and project workflow. <b>A,</b> Overview experimental The study includes primary breast cancer tissue samples with metastases to four different sites (bone, brain, liver, soft tissue). Three antibody panels were used for IMC on consecutive slides, targeting tumor immune phenotypes. <b>B,</b> Targets three their associated function. <b>C,</b> Proportion indicated cell types per patient in after first graph-based...
<p>Phenotypic composition of tumor cells from PT and distant metastasis. <b>A,</b> Left, heatmap showing the median expression level for each cell cluster after flowSOM clustering. Markers used clustering are on <i>x-</i>axis, clusters <i>y-</i>axis. For clustering, all were pooled across samples (<i>n</i> = 87 patients, 559,953 cells), counts in shown (bar plot, gray). Euclidean distance with Ward-D2 linkage was hierarchical rows. Right,...
<p>Spatial T and myeloid CNs are shared between primary tissue metastatic sites. <b>A,</b> Relative enrichment of T-cell (top) (bottom) subtypes in tumor vs. stromal patches across the whole cohort (<i>n</i> = 87). <b>B,</b> Heatmaps illustrating cell-type frequencies per (left), (middle), or cell (right) neighborhood. Columns <i>z</i>-scored for visualization purposes. The corresponding bubble diagrams show significant results (FDR <...
<p>Phenotypic composition analysis of tumor cells between PT and distant metastasis. <b>A,</b> Flow chart depicting the most common phenotypic cluster in vs. metastatic sample. Stacked bar charts show frequency each across patient cohort lines connect matched samples. <b>B,</b> Compositional similarity samples displayed using PCA on per-patient cell abundances as a proportion out all epithelial (abundances were transformed with centered log-ratio...
<p>Immune environment in different metastatic sites and the effect of PT on immune cell composition. <b>A</b> <b>B,</b> T-cell (<b>A</b>) myeloid (<b>B</b>) subtype enrichment or metastasis determined via differential abundance testing using paired design grouped by site metastasis. Bar plot shows log<sub>2</sub>-fold changes (<i>n</i> = 76 patients). <b>C,</b> Boxplot compositional similarity between...
<p>Comparison of the immune environment in PT and metastatic sites. <b>A,</b> Compositional similarity samples displayed using PCA on per-patient cell abundances (<i>n</i> = 76 patients; after applying centered log-ratio transformation). Each point represents a single patient sample either or (M) site. <b>B,</b> Immune type enrichment metastasis determined via differential abundance testing paired design. Bar plot shows...
<p>Supplementary Figures 1-16</p>
<div>Abstract<p>Breast cancer is the most commonly diagnosed in women, with distant metastasis being main cause of breast cancer–related deaths. Elucidating changes tumor and immune ecosystems that are associated metastatic disease essential to improve understanding ultimately treatment metastasis. Here, we developed an in-depth, spatially resolved single-cell atlas phenotypic diversity cells primary human tumors matched metastases, using imaging mass cytometry analyze a total 75...
Abstract Cancer-associated fibroblasts (CAFs) are a diverse cell population within the tumour microenvironment, where they have critical effects on evolution and patient prognosis. To define CAF phenotypes, we analysed single-cell RNA sequencing (scRNA-seq) dataset of over 16,000 stromal cells from tumours 14 breast cancer patients, based which defined functionally annotated nine phenotypes one class pericytes. We validated this classification system in four additional types used highly...