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November 14, 2025Blood Cancer DiscoveryOpen Access

Composition and Functional State of T and NK Cells in the Extramedullary Myeloma Tumor Microenvironment

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Authors

ASAnjana Anilkumar SitharaVKVeronika KapustováDŽDavid Žihala

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Overview

Single-cell profiling reveals an immunosuppressive microenvironment enriched with exhausted T and CD16- NK cells in extramedullary multiple myeloma, indicating mechanisms of treatment resistance.

Key Points

  • To characterize the cellular composition, functional states, and spatial organization of immune cells in extramedullary multiple myeloma lesions relative to paired bone marrow.
  • Profiled the tumor microenvironment in extramedullary multiple myeloma lesions and bone marrow controls using single-cell RNA sequencing, flow cytometry, and spatial transcriptomics.
  • Extramedullary tumors exhibited a significantly lower effector-to-tumor ratio, reduced numbers of CD4+ T cells, and an elevated proportion of regulatory CD16- NK cells compared to bone marrow.
  • Approximately 50% of extramedullary tumors showed a high abundance of exhausted, tumor-reactive CD8+ T cells alongside elevated expression of immune checkpoints, including PD-1 on CD8+ T cells and KLRC1 (NKG2A) on CD16- NK cells.

Cite This Study

Sithara et al. (2025) studied this question.

synapsesocial.com/papers/6a0ceb6ed09dbb66ef026479https://doi.org/10.1158/2643-3230.bcd-25-0170
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Composition and functional state of T and NK cells in the extramedullary myeloma tumor microenvironment2025
  2. 2NK cell dysregulation in the multiple myeloma: insights from multi-modal profiling of the bone marrow microenvironment 28122025
  3. 3Spatial transcriptomics identifies a suppressive, T-cell excluded tumor microenvironment in extramedullary myeloma2026
  4. 4Beyond the marrow: insights from comprehensive next-generation sequencing of extramedullary multiple myeloma tumors2024 · 45 citations
  5. 5Spatially resolved transcriptomics reveals immunosuppressive niches and clonal diversity in extramedullary disease in multiple myeloma refractory to immunotherapy2025