Cutaneous and oral squamous cell carcinoma-dual immunosuppression via recruitment of FOXP3+ regulatory T cells and endogenous tumour FOXP3 expression?

J Craniomaxillofac Surg. 2014 Dec;42(8):1827-33. doi: 10.1016/j.jcms.2014.06.022. Epub 2014 Jul 8.

Abstract

Regulatory T cells (Tregs) are an essential component of the immune system, but are also involved in the suppression of anti-tumour immune responses. The study examines their immunoregulatory role including their transcription factor, FOXP3, in oral and cutaneous SCC. Tregs were detected by double-immunohistochemistry. FOXP3-mRNA-expression was examined in tumour tissue, as well as in skin-derived primary cells and cell lines of different malignancy. Tregs were found in the tumour microenvironment, and FOXP3-mRNA-expression was significantly higher than in normal skin. Intriguingly, single FOXP3(+) cells exhibited morphologic characteristics of SCC cells. Consistent with this, endogenous FOXP3-mRNA-expression was indeed detected in the epidermal cell lineage and dramatically increased with increasing malignancy of the cells. SCCs recruit Tregs into their microenvironment, presumably in order to suppress immunosurveillance, thus avoiding destruction by the immune system. Endogenous FOXP3-expression in malignant epidermoid cells might present a novel mechanism of immune escape.

Keywords: FOXP3; Head and neck cancer; Regulatory T cells; Squamous cell carcinoma; Tregs.

MeSH terms

  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / secondary
  • Cell Line, Tumor
  • Cell Lineage
  • Cell Transformation, Neoplastic / immunology
  • Cells, Cultured
  • Fibroblasts / immunology
  • Forkhead Transcription Factors / immunology*
  • Humans
  • Immune Tolerance / immunology*
  • Immunologic Surveillance / immunology
  • Keratinocytes / immunology
  • Lymphatic Metastasis / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Mouth Neoplasms / immunology*
  • Skin / immunology
  • Skin / pathology
  • Skin Neoplasms / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Escape / immunology
  • Tumor Microenvironment / immunology

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors