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Cancer Prev Res (Phila). 2010 Apr;3(4):438-46. doi: 10.1158/1940-6207.CAPR-09-0194. Epub 2010 Mar 23.

Vaccine against MUC1 antigen expressed in inflammatory bowel disease and cancer lessens colonic inflammation and prevents progression to colitis-associated colon cancer.

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  • 1Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

Abstract

Association of chronic inflammation with an increased risk of cancer is well established, but the contributions of innate versus adaptive immunity are not fully delineated. There has furthermore been little consideration of the role played by chronic inflammation-associated antigens, including cancer antigens, and the possibility of using them as vaccines to lower the cancer risk. We studied the human tumor antigen MUC1 which is abnormally expressed in colon cancers and also in inflammatory bowel disease (IBD) that gives rise to colitis-associated colon cancer (CACC). Using our new mouse model of MUC1(+) IBD that progresses to CACC, interleukin-10 knockout mice crossed with MUC1 transgenic mice, we show that vaccination against MUC1 delays IBD and prevents progression to CACC. One mechanism is the induction of MUC1-specific adaptive immunity (anti-MUC1 IgG and anti-MUC1 CTL), which seems to eliminate abnormal MUC1(+) cells in IBD colons. The other mechanism is the change in the local and the systemic microenvironments. Compared with IBD in vaccinated mice, IBD in control mice is dominated by larger numbers of neutrophils in the colon and myeloid-derived suppressor cells in the spleen, which can compromise adaptive immunity and facilitate tumor growth. This suggests that the tumor-promoting microenvironment of chronic inflammation can be converted to a tumor-inhibiting environment by increasing adaptive immunity against a disease-associated antigen.

(c) 2010 AACR.

Comment in

PMID:
20332301
[PubMed - indexed for MEDLINE]
PMCID:
PMC2853738
Free PMC Article

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