Recent studies have underscored the importance of gamma-delta (γδ) T cells in mediating potent MHC-unrestricted cytotoxicity in numerous malignancies. Here, we analyzed Vδ1 and Vδ2 γδ T cell subsets in newly diagnosed chronic myeloid leukemia (CML) patients (n = 40) who had initiated tyrosine kinase inhibitor (TKI) therapy including imatinib (n = 22), nilotinib (n = 14) and dasatinib (n = 4). Patient peripheral blood samples were analyzed at diagnosis and monitored prospectively at 3, 6, 12 and 18 months post-TKI. γδ T cells isolated from healthy donors and CML patients were used against K562, LAMA-84 and KYO-1 cell lines and against primary CML cells in cytotoxicity assays. We found large expansions of Vδ1 and Vδ2 T cells in patients at diagnosis compared to age-matched healthy donors (n = 40) (p < 0.0001). The γδ T cell reconstitution in patients on imatinib and also on nilotinib showed significant reductions of Vδ1 T cell and Vδ2 T cell absolute counts at 3 months compared to diagnosis. Importantly, Vδ1 and Vδ2 T absolute cell counts remained at normal levels from 3 months throughout the follow-up. Next, we observed susceptibility to specific lysis of primary CML tumor cells by Vδ1 T cells from healthy donors. Furthermore, we determined inherent cytotoxic reactivity by autologous patients' Vδ1 T lymphocytes against primary CML tumor cells. Finally, the TCR clonality profiles showed in CML patients mostly polyclonal repertoires regardless of the TKI. Our results provide further evidence into γδ T cell antileukemia immunity in CML that might be beneficial for long-term disease control and treatment outcome.

• Klíčová slova
• Chronic myeloid leukemia, Clonality, Gamma-delta T cells, Tumor immunotherapy,
• MeSH
• buněčné linie MeSH
• chronická myeloidní leukemie * farmakoterapie   metabolismus   MeSH
• imatinib mesylát farmakologie   terapeutické užití   MeSH
• lidé MeSH
• myeloidní leukemie * metabolismus   MeSH
• receptory antigenů T-buněk gama-delta metabolismus   MeSH
• T-lymfocyty - podskupiny MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imatinib mesylát MeSH
• receptory antigenů T-buněk gama-delta MeSH

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells that has been recognized as a disease responsive to immunotherapy. Despite the huge success of the tyrosine kinase inhibitors (TKIs), CML remains for the most part incurable, probably due to treatment resistance of leukemic stem cells, which are responsible for rapid disease relapse after discontinuation of therapy. Only allogeneic stem cell transplantation enables disease eradication. In addition to the Bcr-Abl1 oncoprotein, TKIs also inhibit off-target kinases (e.g. c-kit, Src, Tec), some of them having physiological functions in immune responses. In vitro studies have implied immunomodulatory effects of TKIs and interferon-alpha (IFN-α), but comprehensive information from in vivo analyses is missing. This review summarizes the recent advances in the field of immunology of CML, including basic information about leukemia-associated antigens and peptide vaccines, that could lead to the incorporation of TKIs and IFN-α in future therapeutic, potentially curative, interventions for CML.

• MeSH
• antigeny nádorové chemie   imunologie   MeSH
• chronická myeloidní leukemie imunologie   terapie   MeSH
• imunitní systém účinky léků   imunologie   MeSH
• imunologické faktory terapeutické užití   MeSH
• imunoterapie MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• interferon alfa metabolismus   terapeutické užití   MeSH
• lidé MeSH
• protinádorové vakcíny imunologie   terapeutické užití   MeSH
• signální transdukce účinky léků   MeSH
• subjednotkové vakcíny imunologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antigeny nádorové MeSH
• imunologické faktory MeSH
• inhibitory proteinkinas MeSH
• interferon alfa MeSH
• protinádorové vakcíny MeSH
• subjednotkové vakcíny MeSH