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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis, Ulcerative / immunology*
  • Colitis, Ulcerative / pathology
  • Colon / immunology
  • Colon / pathology
  • Colorectal Neoplasms / immunology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Disease Models, Animal
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • T-Box Domain Proteins / immunology*


  • DNA-Binding Proteins
  • Rag2 protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21