Increase of NKG2D ligands and sensitivity to NK cell-mediated cytotoxicity of tumor cells by heat shock and ionizing radiation

Exp Mol Med. 2006 Oct 31;38(5):474-84. doi: 10.1038/emm.2006.56.


In this study, we have investigated if current cancer therapeutic modalities including hyperthermia and ionizing radiation can increase the expression of NKG2D ligands in human cancer cell lines. The expressions of NKG2D ligands were induced by both heat shock and ionizing radiation in various cell lines including KM12, NCI-H23, HeLa and A375 cells with peaks at 2 h and 9 h after treatment, respectively, although inducibility of each NKG2D ligand was various depending on cell lines. During the induction of NKG2D ligands, heat shock protein 70 was induced by heat shock but not by ionizing radiation. These results were followed by increased susceptibilities to NK cell-mediated cytolysis after treatment with heat shock and ionizing radiation. These results suggest that heat shock and ionizing radiation induce NKG2D ligands and consequently might lead to increased NK cell-mediated cytotoxicity in various cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Surface / metabolism
  • Antigens, Surface / radiation effects
  • Cytotoxicity, Immunologic / physiology*
  • Cytotoxicity, Immunologic / radiation effects*
  • Gene Expression Regulation, Neoplastic / radiation effects
  • HSP70 Heat-Shock Proteins / metabolism
  • HSP70 Heat-Shock Proteins / radiation effects
  • HeLa Cells
  • Heat-Shock Response* / physiology
  • Hot Temperature
  • Humans
  • Hyperthermia, Induced / methods
  • Killer Cells, Natural / immunology*
  • Ligands*
  • NK Cell Lectin-Like Receptor Subfamily K
  • Neoplasms / immunology
  • Neoplasms / radiotherapy*
  • Neoplasms / therapy
  • Radiation, Ionizing
  • Receptors, Immunologic / metabolism*
  • Receptors, Natural Killer Cell
  • Tumor Cells, Cultured


  • Antigens, Surface
  • HSP70 Heat-Shock Proteins
  • KLRK1 protein, human
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell