Colorectal cancer-derived Foxp3(+) IL-17(+) T cells suppress tumour-specific CD8+ T cells

Scand J Immunol. 2011 Jul;74(1):47-51. doi: 10.1111/j.1365-3083.2011.02539.x.

Abstract

The pathogenesis of cancer is remained to be further understood. This study aims to investigate the role of tumour-derived Foxhead box P3 (Foxp3)(+) interleukin (IL)-17(+) T cells on suppressing tumour-specific CD8(+) T cells. Colorectal cancer (CRC) tissue was collected from surgically removed cancer tissue of 22 patients with CRC. Foxp3(+) IL-17(+) T cells in cancer tissue were examined by flow cytometry. A set of cell markers and cytokines expressed by Foxp3(+) IL-17(+) T cells were determined by immune staining. By coculture with isolated peripheral CD8(+) T cells, the immune regulatory capacity of Foxp3(+) IL-17(+) T cells was examined. The results showed that a number of Foxp3(+) IL-17(+) T cells were found in CRC tissue (22.8 ± 2.6 cells/mm(2) tissue) that was significantly more than in non-cancer colonic mucosa (5.6 ± 1.04 cells/mm(2) tissue). The Foxp3(+) IL-17(+) cells also CD4(+), CCR6(+), transforming growth factor (TGF)-beta(+) and IL-6(+) . The CD8(+) T cells proliferated markedly after exposure to tumour protein in culture that was suppressed in the presence of CRC-derived Foxp3(+) IL-17(+) T cells; the suppression was attenuated by pretreatment with anti-IL-17 antibody. We conclude that CRC-derived Foxp3(+) IL-17(+) T cells have the ability to suppress tumour-specific CD8(+) T cells. This subset of T cells may be a novel therapeutic target in the treatment of CRC.

MeSH terms

  • Adult
  • Aged
  • Antibodies / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Coculture Techniques
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / therapy
  • Female
  • Forkhead Transcription Factors / immunology
  • Humans
  • Immune Tolerance*
  • Immunosuppression Therapy / methods
  • Interleukin-17 / immunology
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / transplantation
  • Tumor Escape

Substances

  • Antibodies
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17