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@article{2233738,
author = {Knight, Andrea and Piskáček, Martin and Jurajda, Michal and Procházková, Jiřina and Ráčil, Zdeněk and Žáčková, Daniela and Mayer, Jiří},
article_location = {NEW YORK},
article_number = {5},
doi = {http://dx.doi.org/10.1007/s00262-022-03312-3},
keywords = {Gamma-delta T cells; Chronic myeloid leukemia; Tumor immunotherapy; Clonality},
language = {eng},
issn = {0340-7004},
journal = {Cancer immunology, immunotherapy},
title = {Expansions of tumor-reactive Vdelta1 gamma-delta T cells in newly diagnosed patients with chronic myeloid leukemia},
url = {https://link.springer.com/article/10.1007/s00262-022-03312-3},
volume = {72},
year = {2023}
}
TY - JOUR
ID - 2233738
AU - Knight, Andrea - Piskáček, Martin - Jurajda, Michal - Procházková, Jiřina - Ráčil, Zdeněk - Žáčková, Daniela - Mayer, Jiří
PY - 2023
TI - Expansions of tumor-reactive Vdelta1 gamma-delta T cells in newly diagnosed patients with chronic myeloid leukemia
JF - Cancer immunology, immunotherapy
VL - 72
IS - 5
SP - 1209-1224
EP - 1209-1224
PB - SPRINGER
SN - 03407004
KW - Gamma-delta T cells
KW - Chronic myeloid leukemia
KW - Tumor immunotherapy
KW - Clonality
UR - https://link.springer.com/article/10.1007/s00262-022-03312-3
N2 - 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.
ER -
KNIGHT, Andrea, Martin PISKÁČEK, Michal JURAJDA, Jiřina PROCHÁZKOVÁ, Zdeněk RÁČIL, Daniela ŽÁČKOVÁ a Jiří MAYER. Expansions of tumor-reactive Vdelta1 gamma-delta T cells in newly diagnosed patients with chronic myeloid leukemia. \textit{Cancer immunology, immunotherapy}. NEW YORK: SPRINGER, 2023, roč.~72, č.~5, s.~1209-1224. ISSN~0340-7004. Dostupné z: https://dx.doi.org/10.1007/s00262-022-03312-3.
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