Targeting NKG2D/NKG2DL axis in multiple myeloma therapy

Cytokine Growth Factor Rev. 2024 Apr:76:1-11. doi: 10.1016/j.cytogfr.2024.02.001. Epub 2024 Feb 15.

Abstract

Immune effector cells in patients with multiple myeloma (MM) are at the forefront of many immunotherapy treatments, and several methods have been developed to fully utilise the antitumour potential of immune cells. T and NK cell-derived immune lymphocytes both expressed activating NK receptor group 2 member D(NKG2D). This receptor can identify eight distinct NKG2D ligands (NKG2DL), including major histocompatibility complex class I (MHC) chain-related protein A and B (MICA and MICB). Their binding to NKG2D triggers effector roles in T and NK cells. NKG2DL is polymorphic in MM cells. The decreased expression of NKG2DL on the cell surface is explained by multiple mechanisms of tumour immune escape. In this review, we discuss the mechanisms by which the NKG2D/NKG2DL axis regulates immune effector cells and strategies for promoting NKG2DL expression and inhibiting its release in multiple myeloma and propose therapeutic strategies that increase the expression of NKG2DL in MM cells while enhancing the activation and killing function of NK cells.

Keywords: NK cell; NKG2D; NKG2DL; multiple myeloma.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunotherapy
  • Killer Cells, Natural
  • Multiple Myeloma* / metabolism
  • Multiple Myeloma* / pathology
  • Multiple Myeloma* / therapy
  • NK Cell Lectin-Like Receptor Subfamily K

Substances

  • NK Cell Lectin-Like Receptor Subfamily K
  • Histocompatibility Antigens Class I