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Increased HLA-DMB expression in the tumor epithelium is associated with increased CTL infiltration and improved prognosis in advanced-stage serous ovarian cancer.

AbstractPURPOSE:
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.
AuthorsMichael 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
JournalClinical 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
PMID19047092 (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.)
Chemical References
  • HLA-D Antigens
  • HLA-DM antigens
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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