Hydroxychloroquine sensitizes chronic myeloid leukemia cells to Vγ9Vδ2 T cell-mediated lysis independent of autophagy

  • Authors:
    • Biqing Han
    • Yanmin Zhao
    • Yu Lin
    • Shan Fu
    • Limengmeng Wang
    • Mingming Zhang
    • Ruxiu Tie
    • Binsheng Wang
    • Yi Luo
    • Lizhen Liu
    • Jian Yu
    • He Huang
  • View Affiliations

  • Published online on: March 24, 2017     https://doi.org/10.3892/ijo.2017.3934
  • Pages: 1810-1820
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Abstract

Hydroxychloroquine (HCQ) is the only autophagy inhibitor in clinical use and it has shown great potential in treating chronic myeloid leukemia (CML). By inhibiting autophagy, HCQ enhances the anti-CML efficiency of chemotherapy. In the present study, we demonstrated that HCQ sensitized CML cells to Vγ9Vδ2 T cell-mediated lysis. HCQ inhibited autophagy in CML cells, but the sensitizing effects of HCQ were autophagy-independent. Since the sensitization was not mimicked by ATG7 knockdown and even occurred in the absence of ATG7. We revealed that in a time-dependent manner HCQ induced the expression of NKG2D ligand ULBP4 on the surface of CML cells. This marks the leukemia cell for recognition by Vγ9Vδ2 T cells. Blocking the interaction of NKG2D with its ligands deleted the sensitizing effects of HCQ. In addition, we showed that HCQ did not affect the synthesis or degradation of ULBP4, but induced the translocation of ULBP4 from the cytoplasm to the cell membrane. Our results uncovered a previously unknown mechanism for HCQ in CML treatment that underlines the ability of HCQ to modulate the immune visibility of CML cells, and pave the way to the development of new combination treatments with HCQ and Vγ9Vδ2 T cells.
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May-2017
Volume 50 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Han B, Zhao Y, Lin Y, Fu S, Wang L, Zhang M, Tie R, Wang B, Luo Y, Liu L, Liu L, et al: Hydroxychloroquine sensitizes chronic myeloid leukemia cells to Vγ9Vδ2 T cell-mediated lysis independent of autophagy. Int J Oncol 50: 1810-1820, 2017.
APA
Han, B., Zhao, Y., Lin, Y., Fu, S., Wang, L., Zhang, M. ... Huang, H. (2017). Hydroxychloroquine sensitizes chronic myeloid leukemia cells to Vγ9Vδ2 T cell-mediated lysis independent of autophagy. International Journal of Oncology, 50, 1810-1820. https://doi.org/10.3892/ijo.2017.3934
MLA
Han, B., Zhao, Y., Lin, Y., Fu, S., Wang, L., Zhang, M., Tie, R., Wang, B., Luo, Y., Liu, L., Yu, J., Huang, H."Hydroxychloroquine sensitizes chronic myeloid leukemia cells to Vγ9Vδ2 T cell-mediated lysis independent of autophagy". International Journal of Oncology 50.5 (2017): 1810-1820.
Chicago
Han, B., Zhao, Y., Lin, Y., Fu, S., Wang, L., Zhang, M., Tie, R., Wang, B., Luo, Y., Liu, L., Yu, J., Huang, H."Hydroxychloroquine sensitizes chronic myeloid leukemia cells to Vγ9Vδ2 T cell-mediated lysis independent of autophagy". International Journal of Oncology 50, no. 5 (2017): 1810-1820. https://doi.org/10.3892/ijo.2017.3934