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

Colorectal cancer‐infiltrating Foxp3+ IL‐17+ T cells promote cancer associated cell marker expression. 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 latterˈs 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‐β, CXCR3, CCR6, and RORγt. 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 tissue‐derived Foxp3+IL‐17+ cells have the capacity to induce cancer‐initiating cells.