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IFN-alfa with dasat...
IFN-alfa with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia
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- Huuhtanen, Jani (author)
- Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Dept Hematol, Helsinki, Finland.;Aalto Univ, Dept Comp Sci, Espoo, Finland.
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- Ilander, Mette (author)
- Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Dept Hematol, Helsinki, Finland.
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- Yadav, Bhagwan (author)
- Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Dept Hematol, Helsinki, Finland.
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- Dufva, Olli M. J. (author)
- Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Dept Hematol, Helsinki, Finland.
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- Lähteenmäki, Hanna (author)
- Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Dept Hematol, Helsinki, Finland.
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- Kasanen, Tiina (author)
- Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Dept Hematol, Helsinki, Finland.
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- Klievink, Jay (author)
- Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Dept Hematol, Helsinki, Finland.
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- Olsson-Strömberg, Ulla (author)
- Uppsala universitet,Hematologi,Uppsala Univ Hosp, Hematol Sect, Uppsala, Sweden.
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- Stentoft, Jesper (author)
- Aarhus Univ Hosp, Dept Hematol, Aarhus, Denmark.
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- Richter, Johan (author)
- Skane Univ Hosp, Dept Hematol Oncol & Radiat Phys, Lund, Sweden.
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- Koskenvesa, Perttu (author)
- Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Dept Hematol, Helsinki, Finland.
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- Höglund, Martin (author)
- Uppsala universitet,Hematologi,Uppsala Univ Hosp, Hematol Sect, Uppsala, Sweden.
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- Söderlund, Stina (author)
- Uppsala universitet,Hematologi,Uppsala Univ Hosp, Hematol Sect, Uppsala, Sweden.
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- Dreimane, Arta (author)
- Linköpings universitet,Institutionen för hälsa, medicin och vård,Medicinska fakulteten,Region Östergötland, Hematologiska kliniken US
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- Porkka, Kimmo (author)
- Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Dept Hematol, Helsinki, Finland.;ICAN Digital Precis Canc Med Flagship, Helsinki, Finland.
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- Gedde-Dahl, Tobias (author)
- Oslo Univ Hosp, Rikshosp, Dept Hematol, Oslo, Norway.
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- Gjertsen, Björn T. (author)
- Univ Bergen, Haukeland Univ Hosp, Hematol Sect, Dept Internal Med, Bergen, Norway.;Univ Bergen, Dept Clin Sci, Bergen, Norway.
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- Stenke, Leif (author)
- Karolinska Institutet
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- Myhr-Eriksson, Kristina (author)
- Sunderby Hosp, Dept Internal Med, Luleå, Sweden.
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- Markevärn, Berit (author)
- Umeå Univ Hosp, Dept Hematol, Umeå, Sweden.
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- Lübking, Anna (author)
- Skane Univ Hosp, Dept Hematol Oncol & Radiat Phys, Lund, Sweden.
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- Dimitrijevic, Andreja (author)
- Odense Univ Hosp, Dept Hematol, Odense, Denmark.
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- Udby, Lene (author)
- Zealand Univ Hosp, Dept Hematol, Roskilde, Denmark.
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- Bjerrum, Ole Weis (author)
- Univ Hosp Copenhagen, Rigshosp, Dept Hematol, Copenhagen, Denmark.
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- Hjorth-Hansen, Henrik (author)
- St Olavs Hosp, Dept Hematol, Trondheim, Norway.;Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, Trondheim, Norway.
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- Mustjoki, Satu (author)
- Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Dept Hematol, Helsinki, Finland.;ICAN Digital Precis Canc Med Flagship, Helsinki, Finland.
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Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Dept Hematol, Helsinki, Finland.;Aalto Univ, Dept Comp Sci, Espoo, Finland. Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Hematol Res Unit Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Dept Hematol, Helsinki, Finland. (creator_code:org_t)
- AMER SOC CLINICAL INVESTIGATION INC, 2022
- 2022
- English.
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In: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 132:17
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Abstract
Subject headings
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- In chronic myeloid leukemia (CML), combination therapies with tyrosine kinase inhibitors (TKIs) aim to improve the achievement of deep molecular remission that would allow therapy discontinuation. IFN-alpha is one promising candidate, as it has long-lasting effects on both malignant and immune cells. In connection with a multicenter clinical trial combining dasatinib with IFN-alpha in 40 patients with chronic-phase CML (NordCML007, NCT01725204), we performed immune monitoring with single-cell RNA and T cell receptor (TCR) sequencing (n = 4, 12 samples), bulk TCR beta sequencing (n = 13, 26 samples), flow cytometry (n = 40, 106 samples), cytokine analyses (n = 17, 80 samples), and ex vivo functional studies (n = 39, 80 samples). Dasatinib drove the immune repertoire toward terminally differentiated NK and CD8+ T cells with dampened functional capabilities. Patients with dasatinib-associated pleural effusions had increased numbers of CD8(+) recently activated effector memory T (Temra) cells. In vitro, dasatinib prevented CD3-induced cell death by blocking TCR signaling. The addition of IFN-alpha reversed the terminally differentiated phenotypes and increased the number of costimulatory intercellular interactions and the number of unique putative epitope-specific TCR clusters. In vitro IFN-alpha had costimulatory effects on TCR signaling. Our work supports the combination of IFN-alpha with TKI therapy, as IFN-alpha broadens the immune repertoire and restores immunological function.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Huuhtanen, Jani
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Ilander, Mette
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Yadav, Bhagwan
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Dufva, Olli M. J ...
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Lähteenmäki, Han ...
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Kasanen, Tiina
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show more...
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Klievink, Jay
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Olsson-Strömberg ...
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Stentoft, Jesper
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Richter, Johan
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Koskenvesa, Pert ...
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Höglund, Martin
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Söderlund, Stina
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Dreimane, Arta
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Porkka, Kimmo
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Gedde-Dahl, Tobi ...
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Gjertsen, Björn ...
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Stenke, Leif
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Myhr-Eriksson, K ...
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Markevärn, Berit
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Lübking, Anna
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Dimitrijevic, An ...
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Udby, Lene
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Bjerrum, Ole Wei ...
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Hjorth-Hansen, H ...
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Mustjoki, Satu
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Journal of Clini ...
- By the university
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Uppsala University
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Linköping University
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Karolinska Institutet