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<p>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.</p>

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Tumour-intrinsic features shape T cell differentiation through precursor to symptomatic multiple myeloma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月5日

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  • Kane A. Foster,
  • Elise Rees,
  • Louise Ainley,
  • Annabel Laidler,
  • Eileen M. Boyle,
  • Lydia Lee,
  • Gwennan Ward,
  • Daria Galas-Filipowicz,
  • Evelyn Fitzsimons,
  • Anna Mikolajczak,
  • Emma J. Lyon,
  • Dylan Jankovic,
  • Jasmine Rahman,
  • Mahima Turakhia,
  • Dipal Mehta,
  • Conor Garrod-Ketchley,
  • Imran Uddin,
  • Gordon Beattie,
  • Yvette Hoade,
  • Catherine Zhu,
  • James L. Reading,
  • Ieuan Walker,
  • Michael Chapman,
  • Karthik Ramasamy,
  • Javier Herrero,
  • Benny Chain,
  • Sergio A. Quezada,
  • Kwee L. Yong

摘要

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.