Cancer Immunology, Immunotherapy

, Volume 58, Issue 5, pp 641–652

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

  • Kui Li
  • Masaki Mandai
  • Junzo Hamanishi
  • Noriomi Matsumura
  • Ayako Suzuki
  • Haruhiko Yagi
  • Ken Yamaguchi
  • Tsukasa Baba
  • Shingo Fujii
  • Ikuo Konishi
Original Article

DOI: 10.1007/s00262-008-0585-3

Cite this article as:
Li, K., Mandai, M., Hamanishi, J. et al. Cancer Immunol Immunother (2009) 58: 641. doi:10.1007/s00262-008-0585-3

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.

Keywords

Ovarian cancer Tumor immunology NKG2D ligand MICA/B ULBP2 

Supplementary material

262_2008_585_MOESM1_ESM.doc (62 kb)
Supplementary table (DOC 62 kb)

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Kui Li
    • 1
    • 2
  • Masaki Mandai
    • 1
  • Junzo Hamanishi
    • 1
  • Noriomi Matsumura
    • 1
  • Ayako Suzuki
    • 1
  • Haruhiko Yagi
    • 1
  • Ken Yamaguchi
    • 1
  • Tsukasa Baba
    • 1
  • Shingo Fujii
    • 3
  • Ikuo Konishi
    • 1
  1. 1.Department of Gynecology and ObstetricsKyoto University Graduate School of MedicineKyotoJapan
  2. 2.Department of Gynecology and ObstetricsPeking University First HospitalBeijingChina
  3. 3.Department of Obstetrics and GynecologyNational Hospital Organization, Kyoto Medical CenterKyotoJapan

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