Increased HLA-DMB expression in the tumor epithelium is associated with increased CTL infiltration and improved prognosis in advanced-stage serous ovarian cancer.
Increased HLA-DMB expression in the tumor epithelium is associated with increased CTL infiltration and improved prognosis in advanced-stage serous ovarian cancer.
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DOI：
10.1158/1078-0432.ccr-08-0479
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发表时间：
2008-12-01
期刊：
影响因子：
--
通讯作者：
Mok SC
中科院分区：
文献类型：
--
作者：
Callahan MJ;Nagymanyoki Z;Bonome T;Johnson ME;Litkouhi B;Sullivan EH;Hirsch MS;Matulonis UA;Liu J;Birrer MJ;Berkowitz RS;Mok SC
To evaluate the possible mechanisms influencing the infiltration of CD8 T lymphocytes into the tumor epithelium of advanced serous ovarian cancers. Immunohistochemical localization of CD8 T lymphocytes was performed on a homogeneous population of 184 high-grade, advanced-stage serous ovarian cancer tissue specimens. Microarray analysis was performed on microdissected tumor epithelium from 38 specimens to identify genes up- or down-regulated in specimens with differing numbers of tumor-infitrating CD8 T lymphocytes. Quantitative real-time polymerase chain reaction and immunohistochemistry were used to validate a candidate gene. Univariate and multivariate survival analyses were performed combining CD8 T lymphocyte number and HLA-DMB expression with standard prognostic factors. Marked CD8 T lymphocyte infiltration of the tumor epithelium is associated with a 20 month improvement in median overall survival. Additionally, when combined with cytoreduction status and age, CD8 T lymphocyte status is an independent prognostic factor for survival. Microarray analysis demonstrated HLA-DMB, a component of the major histocompatibility complex (MHC) II antigen-presentation machinery, to be differentially expressed in specimens with an abundance of tumor-infiltrating CD8 T lymphocytes. This relationship was validated at both the mRNA and protein levels. As well, high HLA-DMB expression in the tumor epithelium was associated with a significant improvement in median overall survival in both univariate and multivariate analyses. Tumor cell expression of HLA-DMB is associated with increased numbers of tumor-infiltrating CD8 T lymphocytes and both are associated with improved survival in advanced serous ovarian cancer.
