Cancer Cell
Volume 16, Issue 3, 8 September 2009, Pages 208-219
Journal home page for Cancer Cell

Article
Colitis-Associated Colorectal Cancer Driven by T-bet Deficiency in Dendritic Cells

https://doi.org/10.1016/j.ccr.2009.07.015Get rights and content
Under an Elsevier user license
open archive

Summary

We previously described a mouse model of ulcerative colitis linked to T-bet deficiency in the innate immune system. Here, we report that the majority of T-bet−/−RAG2−/− ulcerative colitis (TRUC) mice spontaneously progress to colonic dysplasia and rectal adenocarcinoma solely as a consequence of MyD88-independent intestinal inflammation. Dendritic cells (DCs) are necessary cellular effectors for a proinflammatory program that is carcinogenic. Whereas these malignancies arise in the setting of a complex inflammatory environment, restoration of T-bet selectively in DCs was sufficient to reduce colonic inflammation and prevent the development of neoplasia. TRUC colitis-associated colorectal cancer resembles the human disease and provides ample opportunity to probe how inflammation drives colorectal cancer development and to test preventative and therapeutic strategies preclinically.

CELLCYCLE

Cited by (0)

5

Present address: Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37240, USA

6

Present address: Department of Nephrology and Transplantation, King's College London and Guy's and St. Thomas' Hospital, London SE1 9RT, UK

7

Present address: GI Pathology, Boston Caris Diagnostics, 320 Needham Street, Suite 200, Newton, MA 02464, USA