title: Dual Ribosome Profiling uncovers metabolic vulnerabilities in the Tumor Microenvironment of Triple Negative Breast Cancer
creator: Aviles Huerta, Daniela
subject: ddc-570
subject: 570 Life sciences
description: Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited targeted therapy options. Stromal and immune cells densely populate the tumor microenvironment (TME) and are central players in the metabolic reprogramming of cancer. Therefore, elucidating the key metabolic vulnerabilities in the TME, offers new therapeutic perspectives for TNBC. In this study, I introduce the use of Dual Ribosome Profiling (DualRP) as a novel approach for uncovering cell-type specific metabolic limitations in the naïve TME. Firstly, to establish DualRP, systems of ribosomal fluorescent tagging in TNBC cells and fibroblasts were developed and validated. Secondly, DualRP revealed deregulated signaling mechanisms and metabolic interactions in both cell populations interacting simultaneously, which were further validated in vitro and in vivo. Thirdly, DualRP transgenic mouse models confirmed the metabolic vulnerabilities of T cells in TNBC tumors. Lastly, to exploit the metabolic vulnerabilities of TNBC for therapy, the combination of checkpoint inhibition and dietary restriction was applied in vivo. Collectively, my project presents a robust approach to study metabolic vulnerabilities in multiple compartments of the TME simultaneously.
date: 2024
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserver/33886/1/DualRP-Aviles-Daniela-Thesis.pdf
identifier: DOI:10.11588/heidok.00033886
identifier: urn:nbn:de:bsz:16-heidok-338864
identifier:   Aviles Huerta, Daniela  (2024) Dual Ribosome Profiling uncovers metabolic vulnerabilities in the Tumor Microenvironment of Triple Negative Breast Cancer.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/33886/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng