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

J 2023

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

KNIGHT, Andrea, Martin PISKÁČEK, Michal JURAJDA, Jiřina PROCHÁZKOVÁ, Zdeněk RÁČIL et. al.

Basic information

Original name

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

Authors

KNIGHT, Andrea (203 Czech Republic, guarantor, belonging to the institution), Martin PISKÁČEK (40 Austria, belonging to the institution), Michal JURAJDA (203 Czech Republic, belonging to the institution), Jiřina PROCHÁZKOVÁ (203 Czech Republic, belonging to the institution), Zdeněk RÁČIL (203 Czech Republic), Daniela ŽÁČKOVÁ (203 Czech Republic, belonging to the institution) and Jiří MAYER (203 Czech Republic, belonging to the institution)

Edition

Cancer immunology, immunotherapy, NEW YORK, SPRINGER, 2023, 0340-7004

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.800 in 2022

RIV identification code

RIV/00216224:14110/23:00130077

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1007/s00262-022-03312-3

UT WoS

000884524700001

Keywords in English

Gamma-delta T cells; Chronic myeloid leukemia; Tumor immunotherapy; Clonality

Abstract

V originále

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.

Links

NV19-05-00410, research and development project

Name: Úloha cytotoxických gamma-delta T buněk na terapeutické rezistenci a recidivě Glioblastoma Multiforme

Investor: Ministry of Health of the CR

Citovat

KNIGHT, Andrea, Martin PISKÁČEK, Michal JURAJDA, Jiřina PROCHÁZKOVÁ, Zdeněk RÁČIL, Daniela ŽÁČKOVÁ and Jiří MAYER. Expansions of tumor-reactive Vdelta1 gamma-delta T cells in newly diagnosed patients with chronic myeloid leukemia. Cancer immunology, immunotherapy. NEW YORK: SPRINGER, 2023, vol. 72, No 5, p. 1209-1224. ISSN 0340-7004. Available from: https://dx.doi.org/10.1007/s00262-022-03312-3.

@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 and 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, vol.~72, No~5, p.~1209-1224. ISSN~0340-7004. Available from: https://dx.doi.org/10.1007/s00262-022-03312-3.

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