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

被引：154

作者：

Garrett, Wendy S. ^{[1
,2
,4
]}

Punit, Shivesh ^{[1
]}

Gallini, Carey A. ^{[1
]}

Michaud, Monia ^{[1
]}

Zhang, Dorothy ^{[1
]}

Sigrist, Kirsten S. ^{[1
]}

Lord, Graham M. ^{[1
]}

Glickman, Jonathan N. ^{[3
]}

Glimcher, Laurie H. ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA

[4] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

来源：

CANCER CELL | 2009年 / 16卷 / 03期

基金：

美国国家卫生研究院;

关键词：

TOLL-LIKE RECEPTORS; INFLAMMATORY-BOWEL-DISEASE; DNA-PLOIDY PATTERN; ULCERATIVE-COLITIS; COLON CARCINOGENESIS; ALPHA; MODEL; MICE; TUMORIGENESIS; METASTASIS;

D O I：

10.1016/j.ccr.2009.07.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：208 / 219

页数：12

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