Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer: high expression of ULBP2 is an indicator of poor prognosis.
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.
Li
Kui
K
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan.
Mandai
Masaki
M
Hamanishi
Junzo
J
Matsumura
Noriomi
N
Suzuki
Ayako
A
Yagi
Haruhiko
H
Yamaguchi
Ken
K
Baba
Tsukasa
T
Fujii
Shingo
S
Konishi
Ikuo
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018959:CD57 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002277:Carcinoma / Q000737:chemistry* / Q000276:immunology / Q000401:mortality; D017077:Culture Media, Conditioned / Q000737:chemistry; D018572:Disease-Free Survival; D004847:Epithelial Cells / Q000737:chemistry; D005260:Female; D058851:GPI-Linked Proteins; D006680:HLA Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis* / Q000502:physiology; D053208:Kaplan-Meier Estimate; D007694:Killer Cells, Natural / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000502:physiology; D009363:Neoplasm Proteins / Q000032:analysis* / Q000502:physiology; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000276:immunology / Q000401:mortality; D010053:Ovary / Q000737:chemistry; D011379:Prognosis
D018959:CD57 Antigens; D017077:Culture Media, Conditioned; D058851:GPI-Linked Proteins; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D036341:Intercellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009363:Neoplasm Proteins; C423230:ULBP2 protein, human
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