| Description: |
The greatest risk factor for the development of pancreatic cancer is chronic pancreatitis. As such, the transition of chronic pancreatic fibro-inflammatory disease to neoplasia represents a quintessential clinical example in the paradigm of inflammation leading to cancer. However, the cellular and molecular links bridging these entities are not well understood. Since dendritic cells (DC) have recently emerged as initiators of inflammation, we postulated that DC are central in this pancreas-specific process. We found that DC exacerbate pancreatic fibro-inflammation, organ destruction, and accelerate carcinogenesis, even in the absence of an endogenous mutation, by inducing pancreatic antigen-restricted Th2 cells. Furthermore, blockade of MyD88, an adaptor protein central to inflammation and carcinogenesis in other contexts, paradoxically accelerates inflammation and transformation in the pancreas by augmenting the DC-Th2 axis. Our findings are the first to suggest novel pathways that implicate DC and the inhibition of MyD88 in pancreatic inflammation and neoplastic transformation. |
| Relation: |
Bedrosian, Andrea S, Nguyen, Andrew H, Mushlin, Harry M, Hackman, Muchael, Ochi, Atsuo, Connolly, Michael K, Ibrahim, Junaid, Rehman, Adeel, Henning, Justin R, Barilla, Rocky, Pylayeva-Gupta, Yuliya, Mallen-St. Clair, John, Hajdu, Cristina, Frey, Alan B, Bar-Sagi, Dafna and Miller, George (2012) MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells. Journal Experimental Medicine, 209 (9). pp. 1671-1687. ISSN 0022-1007, 1540-9538 |