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PMID: 19732721 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Cancer cell ·Vol. 16 ·No. 3 ·2009-09-08 ·Pages 208-19

Garrett WS, Punit S, Gallini CA, Michaud M, Zhang D, Sigrist KS, Lord GM, Glickman JN, Glimcher LH

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.

MeSH Terms
Animals Colitis, Ulcerative/immunology,pathology Colon/immunology,pathology Colorectal Neoplasms/immunology DNA-Binding Proteins/genetics,metabolism Dendritic Cells/immunology,pathology Disease Models, Animal Humans Immunohistochemistry Mice Mice, Knockout T-Box Domain Proteins/immunology
Chemicals
DNA-Binding Proteins Rag2 protein, mouse T-Box Domain Proteins T-box transcription factor TBX21
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Garrett Wendy S
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA. [email protected]
Punit Shivesh
Gallini Carey A
Michaud Monia
Zhang Dorothy
Sigrist Kirsten S
Lord Graham M
Glickman Jonathan N
Glimcher Laurie H
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Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1878-3686
DOI
10.1016/j.ccr.2009.07.015
Email
[email protected]
Published
2009-09-08
Pages
208-19
Language
English
Region
United States
NLM ID
101130617
PMCID
PMC2740755
Subset
IM
Grants
NCI NIH HHS · R01 CA112663-10 · United States
NCI NIH HHS · R01 CA112663 · United States
NIAID NIH HHS · K08 AI078942 · United States
NCI NIH HHS · CA112663 · United States
Medical Research Council · G0802068 · United Kingdom
NCI NIH HHS · P50 CA127003 · United States
External Links
PubMed source DOI: 10.1016/j.ccr.2009.07.015 PMC Full Text View journal details
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