ArticleHaematologica2023
Differential inhibition of T-cell receptor and STAT5 signaling pathways determines the immunomodulatory effects of dasatinib in chronic phase chronic myeloid leukemia.
Article in Haematologica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 10 citations in OpenAlex.
- Fast Real-Time Assessment of Combination Therapies in Immuno-ONcology in patients with advanced non-small-cell lung cancer (FRACTION-Lung).ESMO open · 2026Trial
- Treatment-free remission and immune profiling after frontline second-generation TKI therapy in CML.Blood advances · 2026Article
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Reconsidering dualTranslational cancer research · 2026Article
- Dasatinib Produces Lengthy Remissions of Extramedullary Leukemia: A Retrospective Observational Study.European journal of haematology · 2026Observational
- TRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation.Life science alliance · 2026Article
- The evolving landscape of regulatory T cells in leukemia: from mechanisms to advanced immunotherapeutic strategies.Frontiers in immunology · 2026Review
- Development of Colonic Polyposis in a Woman With Chronic Myeloid Leukemia Treated With Dasatinib.Case reports in hematology · 2026Article
- Post-Translational Modifications in Cancer-Associated CD8⁺ T-Cell Exhaustion: Mechanisms and Therapeutic Opportunities.International journal of biological sciences · 2026Review
- Single-cell and transcriptomic profiling reveal stemness-driven immune evasion in obstructive sleep apnea (OSA) associated lung cancer.Journal of Cancer · 2026Article
- Innate CD8 T-cells as a potential predictive biomarker for deep molecular response in chronic myeloid leukemia patients.Cancer immunology, immunotherapy : CII · 2025Article
- Advancing our understanding of the influence of myeloid-derived suppressor cells in chronic myeloid leukemia.Journal of cancer research and clinical oncology · 2025Review
- CD8Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dasatinib is a multi-kinase inhibitor with activity against the SRC kinase LCK, which plays a critical role in T-cell receptor signaling. Dasatinib, initially developed as an immunosuppressive agent, is by contrast, also noted to result in enhanced tumor immunity in a subset of patients. We studied the impact of dasatinib in chronic myeloid leukemia patients and compared it with patients taking other tyrosine kinase inhibitors (TKI) and healthy controls. We found that patients on dasatinib showed inhibition of both T-cell receptor (TCR) and STAT5 signaling pathways, and reduced expression of Teffector pro-inflammatory cytokines. In addition, dasatinib induced selective depletion of regulatory T cells (Tregs) and effector Tregs, particularly in patients with clonal expansion of effector CD8+ T cells, who demonstrated greater and preferential inhibition of Treg TCR intracellular signaling. In addition, we show that dasatinib selectively reduces Treg STAT5 phosphorylation via reduction of IL-2, in relation with the marked reduction of plasma IL-2 levels in patients taking dasatinib. Finally, patients on other TKI had significantly increased TCR signaling in TIM3+ cells compared to patients taking dasatinib, suggesting that chronic SRC kinase inhibition by dasatinib may play a role in preventing TIM-3-mediated T-cell exhaustion and preserve anti-tumor immunity. These data provide further insight into the selective immunomodulatory effects of dasatinib and its potential use for pharmacologic control of immunotherapies.
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