Targeting the NKG2D/NKG2D-L axis in acute myeloid leukemia

Biomed Pharmacother. 2021 May:137:111299. doi: 10.1016/j.biopha.2021.111299. Epub 2021 Jan 25.

Abstract

Natural killer group 2, member D (NKG2D) receptor is a crucial activating receptor in the immune recognition and eradication of abnormal cells by natural killer (NK) cells, and T lymphocytes. NKG2D can transmit activation signals and activate the immune system by recognizing the NKG2D ligands (NKG2D-L) on acute myeloid leukemia (AML) cells. Downregulation of NKG2D-L in AML can circumvent resistance to chemotherapy and immune recognition. Considering this effect, the exploration of targeting the NKG2D/NKG2D-L axis is considered to have tremendous potential for the discovery of novel biomacromolecule antibodies and pharmacological modulators in AML. This review was to outline the impact of NKG2D/NKG2D-L axis on intrinsic immunosurveillance and the development of AML. Furthermore, the NKG2D/NKG2D-L axis related modulators and progress in preclinical and clinical trials was also to be reviewed.

Keywords: Acute myeloid leukemia; Immune escape; NK cells; NKG2D/NKG2D-L.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / metabolism
  • Ligands
  • Molecular Targeted Therapy
  • NK Cell Lectin-Like Receptor Subfamily K / antagonists & inhibitors*
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • Signal Transduction
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents
  • KLRK1 protein, human
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K