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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2009 Sep 8

PMID 19732721

Citations 89

Authors

Wendy S Garrett

Shivesh Punit

Carey A Gallini

Monia Michaud

Dorothy Zhang

Kirsten S Sigrist

Graham M Lord

Jonathan N Glickman

Laurie H Glimcher

Affiliations

Soon will be listed here.

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.

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