Tumour-intrinsic features shape T cell differentiation through precursor to symptomatic multiple myeloma
Multiple myeloma (MM) is associated with skewed T cell activation and function which is present in asymptomatic myeloma precursor conditions, but underlying mechanisms of progression remain undefined. Here, we assemble a large single-cell RNA sequencing dataset of the bone marrow and blood from patients with MM, precursor conditions, and non-cancer controls. We demonstrate that, unlike solid cancers, MM is not characterized by T cell exhaustion, but by antigen-driven terminal memory differentiation. This is influenced by tumour-intrinsic features including tumour burden and expression of antigen-presentation genes. Expanded TCR clones accumulating in MM are not enriched with viral specificities but accumulate in effector states in highly-infiltrated marrows. Additionally, we identify a role for T cell dynamics in patients treated with autologous stem cell transplantation and demonstrate T cell features predict progression from precursor to symptomatic MM. Together, these results suggest that anti-tumour immunity drives a distinctive form of cancer-associated T cell differentiation in MM.
Authors
- Anna Mikolajczak (ORCID: https://orcid.org/0009-0002-0603-6867)
- Dylan Jankovic
- Ieuan Walker (ORCID: https://orcid.org/0000-0002-6075-3907)
- Gordon Beattie
- Eileen M. Boyle (ORCID: https://orcid.org/0000-0001-8791-1744)
- Yvette Hoade
- Imran Uddin (ORCID: https://orcid.org/0000-0002-5681-6848)
- Emma J. Lyon (ORCID: https://orcid.org/0009-0004-7264-7177)
- Evelyn Fitzsimons (ORCID: https://orcid.org/0000-0001-9280-9971)
- Catherine Zhu (ORCID: https://orcid.org/0000-0002-8644-1813)
- Chain Benny
- Gwennan Ward
- J. Herrero (ORCID: https://orcid.org/0000-0002-5459-1139)
- Kane Foster (ORCID: https://orcid.org/0000-0002-0330-8305)
- Conor Garrod-Ketchley (ORCID: https://orcid.org/0000-0002-0548-5057)
- Mahima Turakhia
- Louise Ainley (ORCID: https://orcid.org/0000-0003-0630-7065)
- James L. Reading (ORCID: https://orcid.org/0000-0001-5381-978X)
- Karthik Ramasamy
- Jasmine Rahman
- Elise Rees (ORCID: https://orcid.org/0000-0001-8169-0776)
- Annabel Laidler
- Daria Galas-Filipowicz
- Lydia Lee
- Dipal Mehta
- Michael Chapman
- Sergio A. Quezada
- Kwee L. Yong
Institutions
- University College London Hospitals NHS Foundation Trust (GB)
- Cancer Research UK (GB)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- London Cancer (GB)
- The London College (GB)
- Oxford University Hospitals NHS Trust (GB)
- CRUK Lung Cancer Centre of Excellence (GB)
- MRC Toxicology Unit (GB)
- University College London (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-02-05
- DOI
- https://doi.org/10.1038/s41467-026-68718-4
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00