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Understanding dormancy in Glioblastoma

Pöysti, Anni; (2023) Understanding dormancy in Glioblastoma. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Glioblastoma (GBM) is the most common and aggressive form of primary brain cancer. Despite being treated with a combination of surgical resection, chemotherapy and radiation, this devastating disease remains to date incurable with an average survival of 15 months after diagnosis. One of the biggest challenges to the treatment of GBM is its near universal recurrence, which is thought to be driven by a population of Glioblastoma stem-like cells (GSCs). Like normal neural stem cells, and stem-like cells in other cancers, a subpopulation of GSCs has been shown to exist in a slow cycling, dormant state. As chemo- and radiotherapies mainly target rapidly dividing cells, treatments targeting dormant cell populations are currently lacking. Thus, dormancy is thought to play a key role in the maintenance and the therapeutic resistance of the GSC population. Nevertheless, our understanding of how this phenomenon is controlled, and to what extent the dormant tumour cell population overlaps with the GSC pool remains incomplete. By using somatic mouse models of GBM, combined with the inducible H2B-GFP label retention system, we isolated dormant tumour cells from their in vivo niches, and characterised them functionally and by single cell RNA sequencing. This unveiled the existence of a heterogeneous dormant cell population, characterised notably by an increased expression of interferon induced inflammatory genes. By using a combination of in vitro and in vivo approaches, we demonstrated a role of interferons promoting dormancy in GBM, a phenomenon possibly driven by T-cell infiltration.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Understanding dormancy in Glioblastoma
Language: English
Additional information: Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/10178460
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