Abstract | PURPOSE: To evaluate the possible mechanisms influencing the infiltration of CD8 T lymphocytes into the tumor epithelium of advanced-stage serous ovarian cancers. EXPERIMENTAL DESIGN: Immunohistochemical localization of CD8 T lymphocytes was done on a homogeneous population of 184 high-grade, advanced-stage serous ovarian cancer tissue specimens. Microarray analysis was done on microdissected tumor epithelium from 38 specimens to identify genes up-regulated or down-regulated in specimens with differing numbers of tumor-infiltrating CD8 T lymphocytes. Quantitative real-time PCR and immunohistochemistry were used to validate a candidate gene. Univariate and multivariate survival analyses were done combining CD8 T lymphocyte number and HLA-DMB expression with standard prognostic factors. RESULTS: 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 showed HLA-DMB, a component of the 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 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. CONCLUSIONS:
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-stage serous ovarian cancer.
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Authors | Michael J Callahan, Zoltan Nagymanyoki, Tomas Bonome, Michael E Johnson, Babak Litkouhi, Elizabeth H Sullivan, Michelle S Hirsch, Ursula A Matulonis, Joyce Liu, Michael J Birrer, Ross S Berkowitz, Samuel C Mok |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 14
Issue 23
Pg. 7667-73
(Dec 01 2008)
ISSN: 1078-0432 [Print] United States |
PMID | 19047092
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- HLA-D Antigens
- HLA-DM antigens
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Topics |
- Cystadenocarcinoma, Serous
(immunology, metabolism, mortality)
- Epithelium
(immunology, metabolism)
- Female
- Fluorescent Antibody Technique
- HLA-D Antigens
(biosynthesis)
- Humans
- Immunohistochemistry
- Kaplan-Meier Estimate
- Lymphocytes, Tumor-Infiltrating
(immunology)
- Oligonucleotide Array Sequence Analysis
- Ovarian Neoplasms
(immunology, metabolism, mortality)
- Prognosis
- Reverse Transcriptase Polymerase Chain Reaction
- T-Lymphocytes, Cytotoxic
(immunology)
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