Natural killer, but not natural killer T, cells play a necessary role in the promotion of an innate antitumor response induced by IL-18

Wataru Hashimoto, Fumiaki Tanaka, Paul D. Robbins, Masaru Taniguchi, Haruki Okamura, Michael T. Lotze, Hideaki Tahara

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

IL-18 administration promotes innate immunity resulting in significant antitumor effects in multiple murine tumor models. Here, we examined the effector population mediating the innate immunity. Most NK cells and some NKT cells express IL-18Rs without prior stimulation (65% positive in NK cells, 18% positive in NKT cells), though few naive T cells do. In vivo depletion of NK cells, but not NKT cells, using AsGM1 antibody significantly reduces IL-18-induced cytotoxicity. However, NK-like activity of hepatic MNCs for the NK target YAC-1 was present in Vα 14 NKT cell-deficient animals. Furthermore, administration of rIL-18 greatly reduced B16 pulmonary metastases in vivo in NKT cell-deficient animals. When sorted NK and NKT cells were exposed to IL-18 in vitro, NK cells showed more IFN-γ production and cytolysis against YAC-1 than NKT cells in response to IL-18. These results are consistent with the notion that NK cells, but not NKT cells, are the major effectors in IL-18-induced innate immunity.

Original languageEnglish (US)
Pages (from-to)508-513
Number of pages6
JournalInternational Journal of Cancer
Volume103
Issue number4
DOIs
StatePublished - Feb 10 2003

Keywords

  • Cytokine
  • Cytotoxicity
  • IFN-γ
  • Natural killer cell
  • Tumor immunology

Fingerprint Dive into the research topics of 'Natural killer, but not natural killer T, cells play a necessary role in the promotion of an innate antitumor response induced by IL-18'. Together they form a unique fingerprint.

  • Cite this