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Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer: high expression of ULBP2 is an indicator of poor prognosis

Cancer Immunology, Immunotherapy volume 58, pages 641–652 (2009)Cite this article

Abstract

Objective

To investigate the clinical significance of the expression of the NKG2D ligands MICA/B and ULBP2 in ovarian cancer.

Methods

Eighty-two ovarian cancer patients and six patients without ovarian cancer from Department of Obstetrics and Gynecology of Kyoto University Hospital were enrolled in this study between 1993 and 2003. Expression of MICA/B, ULBP2, and CD57 in ovarian cancer tissue and normal ovary tissue was evaluated by immunohistochemical staining, and the relationship of these results to relevant clinical patient data was analyzed. Expression of MICs, ULBP2, and HLA-class I molecules in 33 ovarian cancer cell lines and two normal ovarian epithelial cell lines, as well as levels of soluble MICs and ULBP2 in the culture supernatants, were measured.

Results

Expression of MICA/B and ULBP2 was detected in 97.6 and 82.9% of ovarian cancer cells, respectively, whereas neither was expressed on normal ovarian epithelium. The expression of MICA/B in ovarian cancer was highly correlated with that of ULBP2. Strong expression of ULBP2 in ovarian cancer cells was correlated with less intraepithelial infiltration of T cells and bad prognoses for patients, suggesting that ULBP2 expression is a prognostic indicator in ovarian cancer. The expression of NKG2D ligands did not correlate with the levels of the soluble forms of the ligands.

Conclusions

High expression of ULBP2 is an indicator of poor prognosis in ovarian cancer and may relate to T cell dysfunction in the tumor microenvironment.

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Acknowledgments

The authors thank Dr. Aoki, Keio University Japan; Dr. Saga, Jichi Medical University Japan; Dr. Hirahara, Yokohama City University Japan; Dr. Berchuck and Dr. Murphy, Duke University USA for kindly providing ovarian cell lines.

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Affiliations

  1. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Kui Li, Masaki Mandai, Junzo Hamanishi, Noriomi Matsumura, Ayako Suzuki, Haruhiko Yagi, Ken Yamaguchi, Tsukasa Baba & Ikuo Konishi

  2. Department of Gynecology and Obstetrics, Peking University First Hospital, 1 Xi’an Men Street, Xicheng District, 100034, Beijing, China

    Kui Li

  3. Department of Obstetrics and Gynecology, National Hospital Organization, Kyoto Medical Center, 1-1, Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, 612-8555, Japan

    Shingo Fujii

Authors
  1. Kui Li
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  2. Masaki Mandai
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  3. Junzo Hamanishi
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  9. Shingo Fujii
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Corresponding author

Correspondence to Masaki Mandai.

Additional information

This work was supported by grants from Grant-in-Aid for Scientific Research (19390426, 19591932, 18209052 and 19659421) from the Ministry of Education, Science, Sports, Culture and Technology of Japan.

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Li, K., Mandai, M., Hamanishi, J. et al. Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer: high expression of ULBP2 is an indicator of poor prognosis. Cancer Immunol Immunother 58, 641–652 (2009). https://doi.org/10.1007/s00262-008-0585-3

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  • DOI: https://doi.org/10.1007/s00262-008-0585-3

Keywords

  • Ovarian cancer
  • Tumor immunology
  • NKG2D ligand
  • MICA/B
  • ULBP2