Targeting the αv integrin/TGF-β axis improves natural killer cell function against glioblastoma stem cells

Jun 17, 2021The Journal of clinical investigation

Improving natural killer cell response to brain tumor stem cells by targeting the αv integrin and TGF-β pathway

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Abstract

Glioblastoma stem cells (GSCs) are sensitive to lysis by healthy allogeneic natural killer (NK) cells in vitro.

  • GSCs exhibit resistance to standard therapies, contributing to the recurrence of glioblastoma multiforme (GBM).
  • Mass cytometry and single-cell RNA sequencing show that NK cells in GBM tumors have an altered phenotype with impaired lytic function compared to NK cells from peripheral blood.
  • Direct contact between GSCs and NK cells activates TGF-β via αv integrin, leading to immune evasion by GSCs.
  • Combining allogeneic NK cells with inhibitors of integrin or TGF-β signaling, or using TGFBR2 gene-edited NK cells, prevents GSC-induced dysfunction of NK cells and inhibits tumor growth.
  • The αv integrin/TGF-β axis may represent a therapeutic target for GBM treatment.

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