ArticleCancer immunology research2022
Immune Phenotypes and Target Antigens of Clonally Expanded Bone Marrow T Cells in Treatment-Naïve Multiple Myeloma.
Article in Cancer immunology research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- CAR-modified marrow infiltrating lymphocytes efficiently target malignant plasma cells with very low antigen density.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Review
- Single-cell proteomic analysis reveals Multiple Myeloma heterogeneity and the dynamics of the tumor immune microenvironment in precursor and advanced states.Neoplasia (New York, N.Y.) · 2025Article
- Article
- Endogenous CD4+ T Cells That Recognize ALK and the NPM1::ALK Fusion Protein Can Be Expanded from Human Peripheral Blood.Cancer immunology research · 2025Article
- HLA-C*04:09N is expressed at the cell surface and triggers peptide-specific T-cell activation.Haematologica · 2024Article
- Single-cell genomics-based immune and disease monitoring in blood malignancies.Clinical hematology international · 2024Review
- Review
- Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease.Blood · 2023Article
Corrections and comments
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Authors and funding
22 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma is a hematologic malignancy of monoclonal plasma cells that accumulate in the bone marrow. Despite their clinical and pathophysiologic relevance, the roles of bone marrow-infiltrating T cells in treatment-naïve patients are incompletely understood. We investigated whether clonally expanded T cells (i) were detectable in multiple myeloma bone marrow, (ii) showed characteristic immune phenotypes, and (iii) whether dominant clones recognized antigens selectively presented on multiple myeloma cells. Single-cell index sorting and T-cell receptor (TCR) αβ sequencing of bone marrow T cells from 13 treatment-naïve patients showed dominant clonal expansion within CD8+ cytolytic effector compartments, and only a minority of expanded T-cell clones expressed the classic immune-checkpoint molecules PD-1, CTLA-4, or TIM-3. To identify their molecular targets, TCRs of 68 dominant bone marrow clones from five selected patients were reexpressed and incubated with multiple myeloma and non-multiple myeloma cells from corresponding patients. Only 1 of 68 TCRs recognized antigen presented on multiple myeloma cells. This TCR was HLA-C-restricted, self-peptide-specific and could be activated by multiple myeloma cells of multiple patients. The remaining dominant T-cell clones did not recognize multiple myeloma cells and were, in part, specific for antigens associated with chronic viral infections. In conclusion, we showed that dominant bone marrow T-cell clones in treatment-naïve patients rarely recognize antigens presented on multiple myeloma cells and exhibit low expression of classic immune-checkpoint molecules. Our data provide experimental context for experiences from clinical immune-checkpoint inhibition trials and will inform future T cell-dependent therapeutic strategies.
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