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

Abstract

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-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.

Stress Response Protein Cirp Links Inflammation and Tumorigenesis in Colitis-Associated Cancer

“…In tumor cells, expression of TNFa might be upregulated in a Cirp-independent manner. IL23 and IL17 inhibit antitumor immunity and promote tumorigenesis (6)(7)(8). Expression of IL23 and IL17 was decreased in Cirp À/À tumors and nontumor colons compared with WT counterparts (Fig.…”

“…IL23/IL17 signaling enhances the immunosuppressive activity of regulatory T cells and reduces CD8 þ cells in tumor, leading to enhanced tumor initiation and promotion (6,7). Recently, a study has suggested that colorectal cancer tissue-derived Foxp3 þ IL17 þ cells have the capacity to induce cancer-initiating cells in vitro (8). The most conspicuous link between inflammation and colon cancer is seen in patients with IBD (9), and development of colorectal cancer is one of the most serious complications of IBD, which is also referred to as colitis-associated cancer (CAC; ref.…”

Glioma-derived T Cell Immunoglobulin- and Mucin Domain-containing Molecule-4 (TIM4) Contributes to Tumor Tolerance

“…The mechanism underlying these effects can be mimicked by induction of the hypoxia-inducible factor (HIF), which acts to regulate cellular processes, including glucose metabolism, angiogenesis, cell proliferation, and tissue remodeling (7). Recent reports indicate that hypoxia facilitates the generation of Tregs in tumor tissue (8) or strengthens the function of Tregs (9) in tumors, but the underlying mechanism is incompletely understood.…”

Immunological and Clinical Impact of Cancer Stem Cells in Vulvar Cancer: Role of CD133/CD24/ABCG2-Expressing Cells

“…However, an increase of Tregs is also attributed to the expression of VEGF (32)(33). Intriguingly, recent reports demonstrate that interleukin 17-producing Tregs drive cells to become cancer-initiating cells in colorectal cancer (34). Finally, Tregs indirectly interact with CSCs partially driving the differentiation of tumourassociated macrophages that release TGFβ (35).…”