ArticleThe Journal of experimental medicine2020
Tyrosine kinase inhibitor imatinib augments tumor immunity by depleting effector regulatory T cells.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Comparative effectiveness of several adjuvant therapies for patients with hepatocellular carcinoma with high-risk factors for recurrence after hepatectomy: a systematic review and meta-analysis.Frontiers in medicine · 2025Pooled it
- A lower initial dose of bosutinib for patients with chronic myeloid leukemia patients resistant and/or intolerant to prior therapy: a single-arm, multicenter, phase 2 trial (BOGI trial).International journal of hematology · 2024Trial
- Treatment-free remission and immune profiling after frontline second-generation TKI therapy in CML.Blood advances · 2026Article
- Improved outcomes with TKI maintenance after brexucabtagene autoleucel in Philadelphia chromosome ALL.Blood advances · 2026Article
- Treatment-Free Remission in Chronic Myeloid Leukemia: Toward Precision and Personalized Approaches to Functional Cure.Cancer science · 2026Review
- Ponatinib inhibits LCK and PI3K signaling and promotes CD8Nature communications · 2026Article
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Kinase signaling in the control of regulatory T cell function: molecular mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- From immune desert to hot tumor: the tripartite synergy of tumor microenvironment-exosomes-immunogenic cell death in pioneering solutions.Frontiers in immunology · 2026Review
- Posttransplant cells for the win? DLI and adoptive cell therapy to eradicate MRD.Hematology. American Society of Hematology. Education Program · 2025Review
- Article
- Immunometabolism of regulatory T cells in cancer.Oncogene · 2025Review
- Bosutinib for Successful Treatment-Free Remission in Chronic Myeloid Leukemia.Cancer medicine · 2025Article
- Reshape memory T cell landscape in CML patients' blood by tyrosine kinase inhibitors.Caspian journal of internal medicine · 2025Article
- Imatinib associated discoid lupus erythematosus in a patient with chronic myeloid leukemia.JAAD case reports · 2024Article
- Prognostic Significance of Regulatory T-Cells and PD-1 + CD8 T-Cells in Chronic Myeloid Leukemia Patients Treated with Generic Imatinib.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2024Article
- Lck Function and Modulation: Immune Cytotoxic Response and Tumor Treatment More Than a Simple Event.Cancers · 2024Review
- FOXP3 expression in esophageal squamous cell carcinoma : Implications for cetuximab sensitivity and therapeutic strategies.Wiener klinische Wochenschrift · 2024Article
- Regulatory T cell-mediated immunosuppression orchestrated by cancer: towards an immuno-genomic paradigm for precision medicine.Nature reviews. Clinical oncology · 2024Review
- Establishment of immune suppression by cancer cells in the tumor microenvironment.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2024Article
Corrections and comments
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Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This report addresses whether small molecules can deplete FoxP3-expressing regulatory T (T reg) cells, thereby augmenting antitumor immunity. Imatinib, a tyrosine kinase inhibitor of oncogenic BCR-ABL protein expressed by chronic myelogenous leukemia (CML) cells, possesses off-targets including LCK expressed in T cells. We showed that imatinib-treated CML patients in complete molecular remission (CMR) exhibited selective depletion of effector T reg (eT reg) cells and significant increase in effector/memory CD8+ T cells while non-CMR patients did not. Imatinib at CML-therapeutic concentrations indeed induced apoptosis specifically in eT reg cells and expanded tumor antigen-specific CD8+ T cells in vitro in healthy individuals and melanoma patients, and suppressed colon tumor growth in vivo in mice. Mechanistically, because of FoxP3-dependent much lower expression of LCK and ZAP-70 in T reg cells compared with other T cells, imatinib inhibition of LCK further reduced their TCR signal intensity, rendering them selectively susceptible to signal-deprived apoptotis. Taken together, eT reg cell depletion by imatinib is instrumental in evoking effective immune responses to various cancers.
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