Targeting NK-cell checkpoints for cancer immunotherapy

Curr Opin Immunol. 2017 Apr;45:73-81. doi: 10.1016/j.coi.2017.01.003. Epub 2017 Feb 23.

Abstract

Natural Killer (NK) cells are cytotoxic lymphocytes specialized in early defense against virus-infected and transformed cells. NK-cell function is regulated by activating and inhibitory surface receptors recognizing their ligands on transformed cells. Modulation of NK numbers and/or function by a variety of agents such as cytokines and monoclonal antibodies may result in enhanced anti-tumor activity. Recombinant cytokines (i.e., IL-15 and IL-2), antibodies blocking inhibitory receptors (i.e., KIR, NKG2A and TIGIT) and agonists delivering signals via CD137, NKG2D and CD16 stand out as the most suitable opportunities. These agents can be used to potentiate NKcell- mediated antibody-dependent cellular cytotoxicity (ADCC) against antibody-coated tumor cells, offering potential for multiple combinatorial immunotherapy strategies against cancer.

Publication types

  • Review

MeSH terms

  • Antibodies, Neoplasm / therapeutic use*
  • Antibody-Dependent Cell Cytotoxicity / drug effects
  • Humans
  • Immunotherapy / methods*
  • Interleukin-15 / therapeutic use*
  • Interleukin-2 / therapeutic use*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / pathology
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / immunology
  • Recombinant Proteins / therapeutic use

Substances

  • Antibodies, Neoplasm
  • IL15 protein, human
  • IL2 protein, human
  • Interleukin-15
  • Interleukin-2
  • Receptors, Immunologic
  • Recombinant Proteins