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

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Abstract

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.

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Authors and Affiliations

  1. First Department of Surgery, University of Yamanashi, 1110 Shimokato, Chuo-city, Yamanashi, 409-3898, Japan

    Shinichirou Izawa, Koji Kono, Kousaku Mimura, Yoshihiko Kawaguchi, Mitsuaki Watanabe, Takanori Maruyama & Hideki Fujii

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  1. Shinichirou Izawa
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  2. Koji Kono
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  3. Kousaku Mimura
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  4. Yoshihiko Kawaguchi
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Correspondence to Koji Kono.

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Izawa, S., Kono, K., Mimura, K. et al. H2O2 production within tumor microenvironment inversely correlated with infiltration of CD56dim NK cells in gastric and esophageal cancer: possible mechanisms of NK cell dysfunction. Cancer Immunol Immunother 60, 1801–1810 (2011). https://doi.org/10.1007/s00262-011-1082-7

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