Publication details

Expansions of tumor-reactive Vdelta1 gamma-delta T cells in newly diagnosed patients with chronic myeloid leukemia

Authors

KNIGHT Andrea PISKÁČEK Martin JURAJDA Michal PROCHÁZKOVÁ Jiřina RÁČIL Zdeněk ŽÁČKOVÁ Daniela MAYER Jiří

Year of publication 2023
Type Article in Periodical
Magazine / Source Cancer immunology, immunotherapy
MU Faculty or unit

Faculty of Medicine

Citation
Web https://link.springer.com/article/10.1007/s00262-022-03312-3
Doi http://dx.doi.org/10.1007/s00262-022-03312-3
Keywords Gamma-delta T cells; Chronic myeloid leukemia; Tumor immunotherapy; Clonality
Description Recent studies have underscored the importance of gamma-delta (??) T cells in mediating potent MHC-unrestricted cytotoxicity in numerous malignancies. Here, we analyzed V?1 and V?2 ?? 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. ?? 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 V?1 and V?2 T cells in patients at diagnosis compared to age-matched healthy donors (n?=?40) (p?<?0.0001). The ?? T cell reconstitution in patients on imatinib and also on nilotinib showed significant reductions of V?1 T cell and V?2 T cell absolute counts at 3 months compared to diagnosis. Importantly, V?1 and V?2 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 V?1 T cells from healthy donors. Furthermore, we determined inherent cytotoxic reactivity by autologous patients’ V?1 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 ?? T cell antileukemia immunity in CML that might be beneficial for long-term disease control and treatment outcome.
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