Foxp3+IL‐17+ T cells promote development of cancer‐initiating cells in colorectal cancer

The pathogenesis of CRC remains to be further understood. This study was designed to elucidate the role of Foxp3 IL-17 T cells in the pathogenesis of CRC. Surgically removed CRC tissue was collected from 12 patients with CRC. The frequency and cytokine profile of Foxp3 IL-17 T cells in CRC were examined by flow cytometry. Chemokine CXCL11 was examined in CRC tissue by Western blotting. Treg chemotaxis was examined in a transwell system. The effect of Foxp3 IL-17 T cells on induction of cancer-initiating cells was examined; the latter’s Akt and MAPK activities and colony formation were examined afterward. Abundant Foxp3 IL-17 T cells were detected in CRC tissue that expresses high levels of TGF, CXCR3, CCR6, and ROR t. High levels of CXCL11 were detected in CRC tissue-derived CD68 cells, which had a strong chemotactic effect on Foxp3 Tregs. Hypoxia induced the expression of IL-17 in Foxp3 Tregs; Foxp3 IL-17 T cells were capable of inducing CRC-associated cell markers in BMMo and drove the cells to be cancer-initiating cells. High levels of phosphorylated Akt and MAPK were detected in the induced cancer-initiation cells; the latter has the capability to form a colony. CRC tissuederived Foxp3 IL-17 cells have the capacity to induce cancer-initiating cells. J. Leukoc. Biol. 89: 000–000; 2011.