自然杀伤细胞2D配体MICA/B和ULBP2在卵巢癌中的临床意义：ULBP2高表达是预后不良的一个指标。
Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer: high expression of ULBP2 is an indicator of poor prognosis.
作者信息
Li Kui, Mandai Masaki, Hamanishi Junzo, Matsumura Noriomi, Suzuki Ayako, Yagi Haruhiko, Yamaguchi Ken, Baba Tsukasa, Fujii Shingo, Konishi Ikuo
机构信息
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan.
出版信息
Cancer Immunol Immunother. 2009 May;58(5):641-52. doi: 10.1007/s00262-008-0585-3. Epub 2008 Sep 13.
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.
目的
探讨自然杀伤细胞2D（NKG2D）配体MICA/B和ULBP2在卵巢癌中的表达及其临床意义。
方法
选取1993年至2003年间京都大学医院妇产科的82例卵巢癌患者和6例非卵巢癌患者。采用免疫组织化学染色法评估卵巢癌组织和正常卵巢组织中MICA/B、ULBP2和CD57的表达，并分析这些结果与患者相关临床资料的关系。检测33种卵巢癌细胞系和2种正常卵巢上皮细胞系中MICA、ULBP2和HLA-I类分子的表达，以及培养上清液中可溶性MICA和ULBP2的水平。
结果
分别在97.6%和82.9%的卵巢癌细胞中检测到MICA/B和ULBP2的表达，而在正常卵巢上皮中均未表达。卵巢癌中MICA/B的表达与ULBP2的表达高度相关。卵巢癌细胞中ULBP2的强表达与T细胞上皮内浸润减少及患者预后不良相关，提示ULBP2表达是卵巢癌的一个预后指标。NKG2D配体的表达与配体可溶性形式的水平无关。
结论
ULBP2高表达是卵巢癌预后不良的指标，可能与肿瘤微环境中的T细胞功能障碍有关。
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