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Cancer Cell. 2009 Sep 8;16(3):208-19. doi: 10.1016/j.ccr.2009.07.015.

Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells.

Author information

1
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA. wendy_garrett@dfci.harvard.edu

Abstract

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.

PMID:
19732721
PMCID:
PMC2740755
DOI:
10.1016/j.ccr.2009.07.015
[Indexed for MEDLINE]
Free PMC Article

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