Regulatory T cells, inherited variation, and clinical outcome in epithelial ovarian cancer

Keith L Knutson, Matthew J. Maurer, Claudia C. Preston, Kirsten B. Moysich, Krista Goergen, Kieran M. Hawthorne, Julie M Cunningham, Kunle Odunsi, Lynn C. Hartmann, Kimberly R. Kalli, Ann L Oberg, Ellen L Goode

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The immune system constitutes one of the host factors modifying outcomes in ovarian cancer. Regulatory T cells (Tregs) are believed to be a major factor in preventing the immune response from destroying ovarian cancers. Understanding mechanisms that regulate Tregs in the tumor microenvironment could lead to the identification of novel targets aimed at reducing their influence. In this study, we used immunofluorescence-based microscopy to enumerate Tregs, total CD4 T cells, and CD8<sup>+</sup> cytotoxic T cells in fresh frozen tumors from over 400 patients with ovarian cancer (>80 % high-grade serous). We sought to determine whether Tregs were associated with survival and genetic variation in 79 genes known to influence Treg induction, trafficking, or function. We used Cox regression, accounting for known prognostic factors, to estimate hazard ratios (HRs) associated with T cell counts and ratios. We found that the ratios of CD8 T cells and total CD4 T cells to Tregs were associated with improved overall survival (CD8/Treg HR 0.84, p = 0.0089; CD4/Treg HR 0.88, p = 0.046) and with genetic variation in IL-10 (p = 0.0073 and 0.01, respectively). In multivariate analyses, the associations between the ratios and overall survival remained similar (IL-10 and clinical covariate-adjusted CD8/Treg HR 0.85, p = 0.031; CD4/Treg HR 0.87, p = 0.093), suggesting that this association was not driven by variation in IL-10. Thus, integration of novel tumor phenotyping measures with extensive clinical and genetic information suggests that the ratio of T cells to Tregs may be prognostic of outcome in ovarian cancer, regardless of inherited genotype in genes related to Tregs.

Original languageEnglish (US)
JournalCancer Immunology, Immunotherapy
DOIs
StateAccepted/In press - Aug 23 2015

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Regulatory T-Lymphocytes
T-Lymphocytes
Ovarian Neoplasms
Interleukin-10
Survival
Tumor Microenvironment
Fluorescence Microscopy
Genes
Ovarian epithelial cancer
Immune System
Neoplasms
Multivariate Analysis
Cell Count
Genotype

Keywords

  • CD8
  • Immune suppression
  • Treg
  • Tumor microenvironment

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

Cite this

Regulatory T cells, inherited variation, and clinical outcome in epithelial ovarian cancer. / Knutson, Keith L; Maurer, Matthew J.; Preston, Claudia C.; Moysich, Kirsten B.; Goergen, Krista; Hawthorne, Kieran M.; Cunningham, Julie M; Odunsi, Kunle; Hartmann, Lynn C.; Kalli, Kimberly R.; Oberg, Ann L; Goode, Ellen L.

In: Cancer Immunology, Immunotherapy, 23.08.2015.

Research output: Contribution to journalArticle

Knutson, Keith L ; Maurer, Matthew J. ; Preston, Claudia C. ; Moysich, Kirsten B. ; Goergen, Krista ; Hawthorne, Kieran M. ; Cunningham, Julie M ; Odunsi, Kunle ; Hartmann, Lynn C. ; Kalli, Kimberly R. ; Oberg, Ann L ; Goode, Ellen L. / Regulatory T cells, inherited variation, and clinical outcome in epithelial ovarian cancer. In: Cancer Immunology, Immunotherapy. 2015.
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