eprintid: 35766
rev_number: 15
eprint_status: archive
userid: 8626
dir: disk0/00/03/57/66
datestamp: 2024-12-05 07:54:18
lastmod: 2025-01-20 13:14:39
status_changed: 2024-12-05 07:54:18
type: doctoralThesis
metadata_visibility: show
creators_name: Schwerd-Kleine, Paul Albert Wolfgang
title: Dissecting the Cellular and Molecular Landscape of Inflammatory Breast Cancer through Single-Cell and Spatial Transcriptomics
subjects: ddc-570
divisions: i-140001
adv_faculty: af-14
abstract: Inflammatory Breast Cancer (IBC) is a distinct and aggressive form of breast cancer with rapid onset and poor prognosis. Despite extensive research, its molecular heterogeneity remains unclear. In this thesis, I present the first compre- hensive single-cell and spatial transcriptomic analysis of IBC, comparing IBC to non-IBC patient samples. This approach provided new insights into IBC’s unique biology and confirmed key disease hallmarks at the molecular level.
The study highlights the critical role of the tumour microenvironment (TME) in driving IBC’s aggressive behaviour. Tumour-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) foster an immune-suppressive, pro- angiogenic environment. Dysregulated pathways, including IL-1β expression and NF-κB signalling in myeloid cells, abundant Treg cells and high TGF-β levels, and activated VEGF-PI3K signalling in endothelial cells, suggest potential therapeutic targets within the TME.
By mapping IBC’s cellular composition, this study reveals immune suppression and chronic inflammation as key drivers of its aggressiveness. The abundance of suppressive T cells and immune evasion mechanisms suggests that immunother- apy, including immune checkpoint blockade, potentially in combination with TGF-β inhibition, could offer promising treatment options. Targeting key signalling path- ways in CAFs and myeloid cells may further disrupt inflammatory feedback loops.
This research advances the understanding of IBC by providing a molecular map of its TME and identifying novel therapeutic avenues. Future studies should focus on validating these targets and developing models to explore combination therapies targeting both the tumour and its microenvironment, offering hope for improved treatment outcomes.
date: 2024
id_scheme: DOI
id_number: 10.11588/heidok.00035766
ppn_swb: 1913927202
own_urn: urn:nbn:de:bsz:16-heidok-357666
date_accepted: 2024-11-29
advisor: HASH(0x55602a665ec0)
language: eng
bibsort: SCHWERDKLEDISSECTING
full_text_status: public
place_of_pub: Heidelberg
citation:   Schwerd-Kleine, Paul Albert Wolfgang  (2024) Dissecting the Cellular and Molecular Landscape of Inflammatory Breast Cancer through Single-Cell and Spatial Transcriptomics.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/35766/1/dissertation-paul-schwerd-kleine.pdf