Cancer Immunology, Immunotherapy

, Volume 60, Issue 12, pp 1801–1810 | Cite as

H2O2 production within tumor microenvironment inversely correlated with infiltration of CD56dim NK cells in gastric and esophageal cancer: possible mechanisms of NK cell dysfunction

  • Shinichirou Izawa
  • Koji KonoEmail author
  • Kousaku Mimura
  • Yoshihiko Kawaguchi
  • Mitsuaki Watanabe
  • Takanori Maruyama
  • Hideki Fujii
Original article


Human NK cells can be divided into two subsets, CD56dimCD16(+)NK and CD56brightCD16(−)NK cells, based on their expression of CD56 and CD16. In the present study, we analyzed the relationship between CD56dim/CD56bright NK cells and H2O2 in tumor-infiltrating NK cells in patients with gastric (n = 50) and esophageal (n = 35) cancer. The ratio of CD56dim NK cells infiltrating tumors gradually decreased according to disease progression. H2O2 was abundantly produced within tumor microenvironments, and there was an inverse correlation between CD56dim NK cell infiltration and H2O2 production. CD56dim NK cells are more sensitive to apoptosis induced by physiological levels of H2O2 than CD56bright NK cells. Furthermore, the exposure of NK cells to H2O2 resulted in the impairment of ADCC activity. In conclusion, H2O2 produced within tumor microenvironments inversely correlated with the infiltration of CD56dim NK cells, possibly due to their preferentially induced cell death. These observations may explain one of the mechanisms behind NK cell dysfunction frequently observed in tumor microenvironments.


NK cells CD16 CD56 Gastric cancer Esophageal cancer H2O2 


Conflict of interest

The authors have no conflicts of interest.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Shinichirou Izawa
    • 1
  • Koji Kono
    • 1
    Email author
  • Kousaku Mimura
    • 1
  • Yoshihiko Kawaguchi
    • 1
  • Mitsuaki Watanabe
    • 1
  • Takanori Maruyama
    • 1
  • Hideki Fujii
    • 1
  1. 1.First Department of SurgeryUniversity of YamanashiChuo-cityJapan

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