Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Dasatinib promotes the potential of proliferation and antitumor responses of human γδT cells in a long-term induction ex vivo environment

Leukemia volume 28, pages 206–210 (2014)Cite this article

Subjects

Access through your institution
Buy or subscribe

γδT cells have become the most widely studied immune cell population, which have an important role in tumor immunotherapy, although how to improve its efficacy is of major interest.1, 2 We read with great interest the article by Mustjoki et al.3 on rapid mobilization of cytotoxic lymphocytes induced by dasatinib therapy in leukemia patients.

The authors investigated the effects of tyrosine kinase inhibitors (TKI) imatinib, nilotinib, dasatinib and sunitinib on blood cell dynamics and function. They found dasatinib, a second-generation broad-spectrum TKI, induced a rapid, dose-dependent and substantial mobilization of non-leukemic lymphocytes in blood peaking 1–2 h after an oral intake and enhanced antileukemia immune responses.3 As the authors analyzed the short-term impact of TKI on the function of immune cells including γδT-cells, the questions therefore arise whether TKI could have therapeutic implications in enhancing γδT cell immune responses in a long-term ex-vivo induction environment. We focused on this interesting point and assessed the effects of imatinib, nilotinib and dasatinib on the yield and effector function of ex-vivo-expanded human γδT cells. We believe that it is of interest to disclose such data to increase our knowledge of different TKIs on long-term impact of γδT cells function and expand their roles in immunotherapy.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. Vantourout P, Hayday A . Six-of-the-best: unique contributions of gammadelta T cells to immunology. Nat Rev Immunol 2013; 13: 88–100.

    Article  CAS  Google Scholar 

  2. Hu Y, Cui Q, Gu Y, Sheng L, Wu K, Shi J et al. Decitabine facilitates the generation and immunosuppressive function of regulatory gammadeltaT cells derived from human peripheral blood mononuclear cells. Leukemia 2013; 27: 1580–1585.

    Article  CAS  Google Scholar 

  3. Mustjoki S, Auvinen K, Kreutzman A, Rousselot P, Hernesniemi S, Melo T et al. Rapid mobilization of cytotoxic lymphocytes induced by dasatinib therapy. Leukemia 2013; 27: 914–924.

    Article  CAS  Google Scholar 

  4. Salih J, Hilpert J, Placke T, Grunebach F, Steinle A, Salih HR et al. The BCR/ABL-inhibitors imatinib, nilotinib and dasatinib differentially affect NK cell reactivity. Int J Cancer 2010; 127: 2119–2128.

    Article  CAS  Google Scholar 

  5. Peng B, Hayes M, Resta D, Racine-Poon A, Druker BJ, Talpaz M et al. Pharmacokinetics and pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patients. J Clin Oncol 2004; 22: 935–942.

    Article  CAS  Google Scholar 

  6. Weisberg E, Manley PW, Cowan-Jacob SW, Hochhaus A, Griffin JD . Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat Rev Cancer 2007; 7: 345–356.

    Article  CAS  Google Scholar 

  7. Li H, Pauza CD . Rapamycin increases the yield and effector function of human gammadelta T cells stimulated in vitro. Cancer Immunol Immunother 2011; 60: 361–370.

    Article  CAS  Google Scholar 

  8. Gertner-Dardenne J, Castellano R, Mamessier E, Garbit S, Kochbati E, Etienne A et al. Human Vgamma9Vdelta2 T cells specifically recognize and kill acute myeloid leukemic blasts. J Immunol 2012; 188: 4701–4708.

    Article  CAS  Google Scholar 

  9. Gioia C, Agrati C, Casetti R, Cairo C, Borsellino G, Battistini L et al. Lack of CD27-CD45RA-V gamma 9V delta 2+ T cell effectors in immunocompromised hosts and during active pulmonary tuberculosis. J Immunol 2002; 168: 1484–1489.

    Article  CAS  Google Scholar 

  10. Dieli F, Vermijlen D, Fulfaro F, Caccamo N, Meraviglia S, Cicero G et al. Targeting human {gamma}delta} T cells with zoledronate and interleukin-2 for immunotherapy of hormone-refractory prostate cancer. Cancer Res 2007; 67: 7450–7457.

    Article  CAS  Google Scholar 

  11. Lombardo LJ, Lee FY, Chen P, Norris D, Barrish JC, Behnia K et al. Discovery of N-(2-chloro-6-methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem 2004; 47: 6658–6661.

    Article  CAS  Google Scholar 

  12. Rix U, Hantschel O, Durnberger G, Remsing Rix LL, Planyavsky M, Fernbach NV et al. Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood 2007; 110: 4055–4063.

    Article  CAS  Google Scholar 

  13. Mustjoki S, Ekblom M, Arstila TP, Dybedal I, Epling-Burnette PK, Guilhot F et al. Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy. Leukemia 2009; 23: 1398–1405.

    Article  CAS  Google Scholar 

  14. Kreutzman A, Ladell K, Koechel C, Gostick E, Ekblom M, Stenke L et al. Expansion of highly differentiated CD8+ T-cells or NK-cells in patients treated with dasatinib is associated with cytomegalovirus reactivation. Leukemia 2011; 25: 1587–1597.

    Article  CAS  Google Scholar 

  15. D'Asaro M, La Mendola C, Di Liberto D, Orlando V, Todaro M, Spina M et al. V gamma 9V delta 2T lymphocytes efficiently recognize and kill zoledronate-sensitized, imatinib-sensitive, and imatinib-resistant chronic myelogenous leukemia cells. J Immunol 2010; 184: 3260–3268.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Major Program of Zhejiang Provincial Science and Technology Project (2012C13021-1, 2009C1401) and Zhejiang Provincial Natural Science Foundation of China (Y2110152, Z2100097), and the Province and the Ministry Fund (WKJ2011-2-001). We appreciate Novartis Pharma for providing zoledronic acid, imatinib, nilotinib and BristolMyers Squibb for providing dasatinib for this research.

Author information

Author notes

  1. K-n Wu, Y-j Wang and Y He: These authors contributed equally to this work.

Authors and Affiliations

  1. Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    K-n Wu, Y-j Wang, Y He, Y-x Hu, H-r Fu, L-x Sheng, B-s Wang, S Fu & H Huang

Authors
  1. K-n Wu
    View author publications

    Search author on:PubMed Google Scholar

  2. Y-j Wang
    View author publications

    Search author on:PubMed Google Scholar

  3. Y He
    View author publications

    Search author on:PubMed Google Scholar

  4. Y-x Hu
    View author publications

    Search author on:PubMed Google Scholar

  5. H-r Fu
    View author publications

    Search author on:PubMed Google Scholar

  6. L-x Sheng
    View author publications

    Search author on:PubMed Google Scholar

  7. B-s Wang
    View author publications

    Search author on:PubMed Google Scholar

  8. S Fu
    View author publications

    Search author on:PubMed Google Scholar

  9. H Huang
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to H Huang.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, Kn., Wang, Yj., He, Y. et al. Dasatinib promotes the potential of proliferation and antitumor responses of human γδT cells in a long-term induction ex vivo environment. Leukemia 28, 206–210 (2014). https://doi.org/10.1038/leu.2013.221

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/leu.2013.221

This article is cited by

Search

Advanced search

Quick links