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

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.