ArticleLeukemia2016
Multiple myeloma causes clonal T-cell immunosenescence: identification of potential novel targets for promoting tumour immunity and implications for checkpoint blockade.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.
What it found
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Who cites it
131 citing papers in PubMed, 192 citations in OpenAlex.
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Multiple Myeloma Cells Resistant to T-cell Therapies Exhibit a CD45+ Immunoevasive Phenotype.Cancer immunology research · 2026Article
- Extracellular Vesicles as Master Regulators of Immune Modulation in Multiple Myeloma.International journal of molecular sciences · 2026Review
- Navigating the Therapeutic Landscape of Multiple Myeloma: Immunotherapy, Microenvironment, and Resistance.Biomedicines · 2026Review
- Beyond exhaustion: T cell fitness for next generation of immunotherapy for hematological cancer.Frontiers in immunology · 2026Review
- Review
- Immunosenescence in aging and neurodegenerative diseases: evidence, key hallmarks, and therapeutic implications.Translational neurodegeneration · 2025Review
- Limitations of CAR-T-Cell Therapy in Hematologic Malignancies: Focusing on Antigen Escape and T-Cell Dysfunction.International journal of molecular sciences · 2025Review
- Vaccination in Multiple Myeloma: Challenges and Strategies.European journal of haematology · 2025Review
- Altered dynamics of T cell subsets in peripheral blood impacts disease progression in newly diagnosed multiple myeloma.Biochemistry and biophysics reports · 2025Article
- Immunosenescence and the Geriatric Giants: Molecular Insights into Aging and Healthspan.Medical sciences (Basel, Switzerland) · 2025Review
- The Evolving Landscape in Multiple Myeloma: From Risk Stratification to T Cell-Directed Advanced Therapies.Cancers · 2025Review
- Single-cell analysis of the T-cell receptor repertoire in untreated myeloma patients suggests potential myelomareactive CD8Haematologica · 2025Article
- Allogeneic chimeric antigen receptors (CARs) as an "off-the-shelf" therapy in multiple myeloma.Immunotherapy · 2025Review
- T Cells Dysfunction in Multiple Myeloma.ImmunoTargets and therapy · 2025Review
- The Role of Senescence, its Therapeutic Relevance and Clinical Implications in the Tumor Microenvironment.Theranostics · 2025Review
- Impact of T cell characteristics on CAR-T cell therapy in hematological malignancies.Blood cancer journal · 2024Review
- Preclinical evaluation of the CD38-targeting engineered toxin body MT-0169 against multiple myeloma.HemaSphere · 2024Article
- Review
- Just scratching the surface: novel treatment approaches for multiple myeloma targeting cell membrane proteins.Nature reviews. Clinical oncology · 2024Review
71 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumour-induced dysfunction of cytotoxic T cells in patients with multiple myeloma (MM) may contribute to immune escape and be responsible for the lack of therapeutic efficacy of immune checkpoint blockade. We therefore investigated dysfunctional clonal T cells in MM and demonstrated immunosenescence but not exhaustion as a predominant feature. T-cell clones were detected in 75% of MM patients and their prognostic significance was revalidated in a new post-immunomodulatory drug cohort. The cells exhibited a senescent secretory effector phenotype: KLRG-1+/CD57+/CD160+/CD28-. Normal-for-age telomere lengths indicate that senescence is telomere independent and potentially reversible. p38-mitogen-activated protein kinase, p16 and p21 signalling pathways known to induce senescence were not elevated. Telomerase activity was found to be elevated and this may explain how normal telomere lengths are maintained in senescent cells. T-cell receptor signalling checkpoints were normal but elevated SMAD levels associated with T-cell inactivation were detected and may provide a potential target for the reversal of clonal T-cell dysfunction in MM. Low programmed death 1 and cytotoxic T-lymphocyte-associated antigen 4 expression detected on T-cell clones infers that these cells are not exhausted but suggests that there would be a suboptimal response to immune checkpoint blockade in MM. Our data suggest that other immunostimulatory strategies are required in MM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.