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Soluble NKG2D ligands impair CD8+ T cell antitumor function dependent of NKG2D downregulation in neuroblastoma

  • Authors:
    • Yi Zhang
    • Feifei Luo
    • Kuiran Dong
  • View Affiliations

  • Published online on: May 24, 2023     https://doi.org/10.3892/ol.2023.13883
  • Article Number: 297
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

T cell‑based immunotherapy has achieved remarkable beneficial clinical outcomes. Tumor‑derived NKG2D ligands (NKG2DL) allow tumors to escape immunologic surveillance. However, the mechanism underlying NKG2DL‑mediated immune escape in neuroblastoma (NB) remains incompletely understood. In the present study, first soluble NKG2DL, soluble major histocompatibility complex (MHC) class‑I‑related chain A and soluble UL‑16 binding proteins expression levels were determined in both the serum from patients with NB and in NB cell line culture supernatants. NB cell‑derived sNKG2DL was initially cleaved by ADAM10 and ADAM17. Furthermore, sNKG2DL expression levels were positively correlated with the immunosuppressive microenvironment and poor prognosis. Tumor‑derived sNKG2DL induced degradation of NKG2D on CD8+ T cells and impaired CD8+ T cell proliferation, IFN‑γ production, and CD107a translocation. More importantly, blockage of sNKG2DL increased the antitumor activity of CD8+ T cells. Thus, the results showed that NB‑induced immunosuppression was achieved through tumor‑derived sMICA and sULBP‑2, and blockage of the tumor‑derived sNKG2DLs with sNKG2DL neutralizing antibodies was a novel strategy to recover T‑cell function and enhance antitumor immunotherapy.
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July-2023
Volume 26 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Zhang Y, Luo F and Dong K: Soluble NKG2D ligands impair CD8<sup>+</sup> T cell antitumor function dependent of NKG2D downregulation in neuroblastoma. Oncol Lett 26: 297, 2023
APA
Zhang, Y., Luo, F., & Dong, K. (2023). Soluble NKG2D ligands impair CD8<sup>+</sup> T cell antitumor function dependent of NKG2D downregulation in neuroblastoma. Oncology Letters, 26, 297. https://doi.org/10.3892/ol.2023.13883
MLA
Zhang, Y., Luo, F., Dong, K."Soluble NKG2D ligands impair CD8<sup>+</sup> T cell antitumor function dependent of NKG2D downregulation in neuroblastoma". Oncology Letters 26.1 (2023): 297.
Chicago
Zhang, Y., Luo, F., Dong, K."Soluble NKG2D ligands impair CD8<sup>+</sup> T cell antitumor function dependent of NKG2D downregulation in neuroblastoma". Oncology Letters 26, no. 1 (2023): 297. https://doi.org/10.3892/ol.2023.13883