ArticleBlood cancer discovery2026
Composition and Functional State of T and NK Cells in the Extramedullary Myeloma Tumor Microenvironment.
Article in Blood cancer discovery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Advances in natural killer cell immunotherapy for hematologic malignancies.Cancer biology & therapy · 2026Review
- Spatial transcriptomics identifies a suppressive, T-cell-excluded tumor microenvironment in extramedullary myeloma.Blood advances · 2026Article
- Review
- CD19 CAR T-cell outcomes in relapsed/refractory extramedullary B-ALL: a multisite, retrospective cohort review.Blood advances · 2026Article
- Whole-genome sequencing of cell-free DNA for assessment of minimal residual disease in high-risk smoldering multiple myeloma.HemaSphere · 2026Article
Corrections and comments
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Authors and funding
32 authors.
Funding
Abstract
Extramedullary multiple myeloma (EMM) is a high-risk feature of multiple myeloma associated with increased resistance to treatments, including modern immunotherapies, and shorter survival. The composition and functional state of immune cells within the EMM tumor microenvironment (TME) remain poorly understood. Using single-cell RNA sequencing, flow cytometry, and spatial transcriptomics, we revealed significant differences in the EMM TME compared with multiple myeloma bone marrow (BM). T and NK cells were verified as the most abundant immune subsets in the EMM TME. Compared with the BM counterparts, we found these tumors to have a significantly reduced effector-to-tumor cell ratio, a significantly lower number of CD4+ T cells, and an increased proportion of regulatory CD16- NK cells. We observed a high proportion of exhausted, tumor-reactive CD8+ T cells in roughly half of EMM tumors. Furthermore, we identified elevated expression of immune checkpoints, such as PD-1 on CD8+ T cells and KLRC1 (NKG2A) on CD16- NK cells. SIGNIFICANCE: This study characterizes the TME in EMM lesions and paired BM from patients with multiple myeloma, revealing a high proportion of less cytotoxic CD16- NK cells in EMM tumors and suggesting that direct cell-cell interactions may underlie the CD8+ T-cell exhaustion observed in a subset of these tumors.
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Registered trials
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