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



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

Faculty of Medicine

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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