Evolving immunosuppressive microenvironment during human cervical carcinogenesis

Mucosal Immunol. 2008 Sep;1(5):412-20. doi: 10.1038/mi.2008.33. Epub 2008 Jul 2.


Chronic infection with human papillomavirus (HPV) can result in cervical cancer. To understand how HPV escapes immune eradication, we examined biophenotypes of immune cells in human normal cervix, cervical intraepithelial neoplasia (CIN), and cancer. Expression and cellular localization of Forkhead box protein-3 (FOXP3), indolamine 2,3-dioxygenase (IDO), interleukin (IL)-10, and interferon (IFN)-gamma were examined by immunofluorescence and immunohistochemistry. Mean cell densities of stromal FOXP3+ cells, IDO+ cells, IL-10+ cells, CD1a+ cells, and macrophages significantly increased from normal cervix to cancer, whereas densities of IFN-gamma+ and MMP-9+ cells increased from normal cervix to CIN but decreased in cancer. Flow cytometry confirmed significant elevation of cervical T cells expressing IFN-gamma and transforming growth factor-beta in CIN compared with normal cervix. Upon activation, a significantly increased proportion of cervical T cells expressed IFN-gamma in CIN than normal. A unique subset of morphologically immature stromal dendritic cells expressing IL-10 and IDO was more numerous in cancer than in normal cervix and CIN. The potentially suppressive immune milieu in the cervix may be permissive of HPV-associated cervical carcinogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Transformation, Neoplastic / immunology*
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Cervix Uteri / immunology
  • Cervix Uteri / metabolism
  • Dendritic Cells / immunology
  • Female
  • Humans
  • Immune Tolerance / immunology*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Macrophages / immunology
  • Middle Aged
  • Papillomaviridae / genetics
  • Phenotype
  • T-Lymphocytes / immunology
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology


  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interleukin-10
  • Interferon-gamma