Ovarian cancer tumor infiltrating T-regulatory (T(reg)) cells are associated with a metastatic phenotype.

Journal Article

OBJECTIVE: The objective of this study was to examine the clinicopathologic correlates of T-regulatory (T(reg)) cell infiltration in serous ovarian cancers and to define gene signatures associated with high T(reg)s. METHODS: Tumor infiltrating T(reg) and cytotoxic T-cells (CTLs) were quantitated in 232 primary serous ovarian cancers by immunostaining for FOXP3 and CD8. Expression microarray analysis was performed in a subset of 48 advanced cancers with the highest and lowest numbers of infiltrating T(reg)s and a genomic signature was developed using binary regression. ANOVA analysis was performed to assess the most differentially expressed genes and these genes were further assessed using Ingenuity Pathway Analysis (IPA) software. RESULTS: High T(reg) infiltration in ovarian cancers was associated with high grade (p<0.0001), advanced stage (p=0.004) and suboptimal debulking (p<0.04), but not with survival. In contrast, high tumor infiltrating CD8 CTL infiltration was associated with favorable survival (median survival 48.7 vs. 34.6 months, p=0.01). A microarray-based genomic signature for high tumor-infiltrating T(reg) cells had a 77% predictive accuracy using leave-one-out cross-validation. ANOVA of microarray data revealed the antigen presentation pathway as the most differentially expressed canonical pathway (p<0.00001) between cancers with high and low T(reg) cells. CONCLUSIONS: These data suggest that there may be an association between increased T(reg) cell infiltration in ovarian cancers and advanced stage. Increased T(reg) infiltration is characterized by a genomic signature enriched with several immunologic pathway genes. Therapeutic strategies that reduce tumor infiltrating T(reg) cells are under investigation and may prove useful in ovarian cancers with high numbers of these cells.

Full Text

Duke Authors

Cited Authors

  • Barnett, JC; Bean, SM; Whitaker, RS; Kondoh, E; Baba, T; Fujii, S; Marks, JR; Dressman, HK; Murphy, SK; Berchuck, A

Published Date

  • March 2010

Published In

Volume / Issue

  • 116 / 3

Start / End Page

  • 556 - 562

PubMed ID

  • 20006900

Electronic International Standard Serial Number (EISSN)

  • 1095-6859

Digital Object Identifier (DOI)

  • 10.1016/j.ygyno.2009.11.020

Language

  • eng

Conference Location

  • United States