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The Tyrosine Kinase...
The Tyrosine Kinase Inhibitors Imatinib and Dasatinib Reduce Myeloid Suppressor Cells and Release Effector Lymphocyte Responses
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- Christiansson, Lisa (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Söderlund, Stina (författare)
- Uppsala universitet,Klinisk immunologi,Hematologi
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- Mangsbo, Sara (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Hjorth-Hansen, Henrik (författare)
- St Olavs Hosp, Dept Hematol, Trondheim, Norway.;Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, Trondheim, Norway.
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- Höglund, Martin (författare)
- Uppsala universitet,Hematologi
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- Markevärn, Berit (författare)
- Department of Hematology, Norrland University Hospital, Umeå, Sweden,Norrland Univ Hosp, Dept Hematol, Umea, Sweden.
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- Richter, Johan (författare)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Stenke, Leif (författare)
- Karolinska Institutet
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- Mustjoki, Satu (författare)
- Univ Helsinki, Dept Med, Div Hematol, Hematol Res Unit Helsinki, Helsinki, Finland.;Univ Helsinki
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- Loskog, Angelica (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Olsson-Strömberg, Ulla (författare)
- Uppsala universitet,Hematologi
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(creator_code:org_t)
- American Association for Cancer Research, 2015
- 2015
- Engelska.
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Ingår i: Molecular Cancer Therapeutics. - : American Association for Cancer Research. - 1535-7163 .- 1538-8514. ; 14:5, s. 1181-1191
- Relaterad länk:
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Immune escape mechanisms promote tumor progression and are hurdles of cancer immunotherapy. Removing immunosuppressive cells before treatment can enhance efficacy. Tyrosine kinase inhibitors (TKI) may be of interest to combine with immunotherapy, as it has been shown that the inhibitor sunitinib reduces myeloid suppressor cells in patients with renal cell carcinoma and dasatinib promotes expansion of natural killer-like lymphocytes in chronic myeloid leukemia (CML). In this study, the capacity of dasatinib and imatinib to reduce myeloid suppressor cells and to induce immunomodulation in vivo was investigated ex vivo. Samples from CML patients treated with imatinib (n = 18) or dasatinib (n = 14) within a Nordic clinical trial (clinicalTrials.gov identifier: NCT00852566) were investigated for the presence of CD11b(+)CD14(-)CD33(+) myeloid cells and inhibitorymolecules (arginase I, myeloperoxidase, IL10) as well as the presence of natural killer cells, T cells (naive/memory), and stimulatory cytokines (IL12, IFN gamma, MIG, IP10). Both imatinib and dasatinib decreased the presence of CD11b(+)CD14(-)CD33(+) myeloid cells as well as the inhibitory molecules and the remaining myeloid suppressor cells had an increased CD40 expression. Monocytes also increased CD40 after therapy. Moreover, increased levels of CD40, IL12, natural killer cells, and experienced T cells were noted after TKI initiation. The presence of experienced T cells was correlated to a higher IFNg and MIG plasma concentration. Taken together, the results demonstrate that both imatinib and dasatinib tilted the immunosuppressive CML tumor milieu towards promoting immune stimulation. Hence, imatinib and dasatinib may be of interest to combine with cancer immunotherapy. (C) 2015 AACR.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
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Till lärosätets databas
- Av författaren/redakt...
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Christiansson, L ...
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Söderlund, Stina
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Mangsbo, Sara
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Hjorth-Hansen, H ...
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Höglund, Martin
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Markevärn, Berit
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visa fler...
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Richter, Johan
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Stenke, Leif
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Mustjoki, Satu
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Loskog, Angelica
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Olsson-Strömberg ...
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Hematologi
- Artiklar i publikationen
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Molecular Cancer ...
- Av lärosätet
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Umeå universitet
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Uppsala universitet
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Karolinska Institutet
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Lunds universitet