Tuning Natural Killer Cell Anti-multiple Myeloma Reactivity by Targeting Inhibitory Signaling via KIR and NKG2A

Front Immunol. 2018 Dec 4;9:2848. doi: 10.3389/fimmu.2018.02848. eCollection 2018.


Natural killer (NK) cells are attractive candidates for allogeneic cell-based immunotherapy due to their potent antitumor effector function and good safety profile. NK cells express killer immunoglobulin-like receptors (KIRs) and the NKG2A receptor important for NK cells education as well as providing inhibitory signals upon encountering HLA-expressing target cells. Multiple myeloma (MM) is an example of a tumor expressing relatively high levels of HLA molecules. In this review, we discuss the functional relevance of inhibitory KIRs and NKG2A for NK cells anti-MM response and strategies to lower these inhibitory signaling to enhance clinical efficacy of allogeneic NK cells in MM.

Keywords: HLA class I; HLA-E; KIR; NK cell; NKG2A; immunotherapy; multiple myeloma.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Killer Cells, Natural / immunology*
  • Multiple Myeloma / immunology*
  • NK Cell Lectin-Like Receptor Subfamily C / immunology*
  • Receptors, KIR / immunology*


  • NK Cell Lectin-Like Receptor Subfamily C
  • Receptors, KIR