Foster, Kane Andrew;
(2025)
Features of T cell differentiation and the T cell receptor repertoire associated with disease evolution in multiple myeloma.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Multiple myeloma (MM) is associated with altered T cell activation and function which is detectable in asymptomatic myeloma precursor conditions. However, the alterations to T cell differentiation that underlie functional changes, how they relate to tumour biology, and what influences the high inter-patient immune variability remains largely unknown. In this thesis, I construct a large dataset of published and newlygenerated single cell RNA and TCR-sequencing of the bone marrow and peripheral blood from patients with MM, precursor conditions, and age-matched controls. I show that, unlike solid cancers, MM is not associated with T cell exhaustion and instead defined by a pattern of T cell differentiation resembling antigen-driven terminal memory differentiation. Myeloma-associated T cell differentiation was associated with tumour-intrinsic features including tumour burden and antigenpresentation genes. Expanded TCR clones accumulating in myeloma were not associated with viral specificities and were enriched in effector states in highlyinfiltrated marrows. Together, these results suggest anti-tumour immunity drives a novel form of cancer-associated T cell differentiation through myeloma disease evolution.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Features of T cell differentiation and the T cell receptor repertoire associated with disease evolution in multiple myeloma |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2025. 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 |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10204948 |
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