Roles for the chemokine receptor CCR6 in pancreatitis and pancreas cancer

---

Presentation Time: 02:45 PM - 03:00 PM
Abstract ID: 5421 - B

Presenting Author:
Donovan Drouillard , MSTP Student at Med. Col. of Wisconsin

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) has a poor average life expectancy of ten months, in large part due to the immunosuppression surrounding the tumor preventing effective anti-tumor immune responses. A mediator of PDAC immunosuppression is regulatory T cells (Tregs). Conversely, pancreatitis is an inflammatory disease and is the leading risk factor for developing PDAC yet is lacking in Tregs. My preliminary data show that CCR6+ Th17 T cells are enriched in pancreatitis, while CCR6+ Tregs are enriched within PDAC tumors with little Th17s. Comparison of CCR6+ Tregs to CCR6- Tregs in PDAC show upregulation of genes involved in activation and suppressive function in the CCR6+ population with reliance on the RORyt and RORA transcription factors. The data suggest that CCR6+ Tregs possess superior suppressive capability and are derived from Th17s. The only ligand for CCR6 is CCL20, which is upregulated in both pancreatitis and PDAC and is correlated with a worse prognosis in PDAC. In pancreatitis, CCL20 is produced by Th17s and macrophages, while in PDAC the CCL20 is produced largely by the basal subtype of PDAC tumor cells. Using mouse models of PDAC, we demonstrated that knock-out of CCR6 resulted in beneficial increase of anti-tumorigenic immune populations within PDAC tumors. Cumulatively, these data support the notion that CCR6 is viable as both a treatment for pancreatitis and as an adjuvant to improve the efficacy of immunotherapy in PDAC.