Influence of hypoxia inducible factors on the immune microenvironment in ovarian cancer

Anticancer Res. 2014 Jun;34(6):2811-9.

Abstract

Background: Ovarian tumors remain immunogenic even at advanced stages, but cancer-induced immunosuppression abrogates immune surveillance. The composition of the immune microenvironment in ovarian tumors was characterized by analyzing selected immunosuppressive factors in specimens from cancer patients. The influence of the hypoxia inducible factors on the immune microenvironment was also addressed.

Materials and methods: Tumor tissue was collected from 21 ovarian cancer patients immediately following tumor excision during surgery. The mRNA expression of selected genes was quantified, and tumor infiltrating leukocytes were characterized by flow cytometry to identify regulatory T-cells, myeloid-derived suppressor cells, and type-2 macrophages.

Results: Overall, a pronounced heterogeneity was found among the analyzed samples. Nevertheless, statistical analysis revealed that the expression of hypoxia inducible factors correlated with the transcription levels of several immunosuppressive molecules.

Conclusion: The activity of hypoxia inducible factors contributes to cancer immunosuppression in ovarian cancer patients.

Keywords: Cancer immunosuppression; cancer hypoxia; human ovarian cancer; immune microenvironment; surgical specimen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma, Mucinous / immunology
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / pathology
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Biomarkers, Tumor / metabolism
  • Cystadenocarcinoma, Serous / immunology
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / pathology
  • Endometrial Neoplasms / immunology
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Female
  • Flow Cytometry
  • Humans
  • Hypoxia*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Immunosuppression Therapy
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Middle Aged
  • Myeloid Cells / immunology*
  • Neoplasm Grading
  • Neoplasm Staging
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Microenvironment

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • endothelial PAS domain-containing protein 1