Vaccine against MUC1 Antigen Expressed in Inflammatory Bowel Disease and Cancer Lessens Colonic Inflammation and Prevents Progression to Colitis-Associated Colon Cancer
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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DOI：
10.1158/1940-6207.capr-09-0194
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发表时间：
2010-04-01
影响因子：
3.3
通讯作者：
Finn, Olivera J.
中科院分区：
文献类型：
--
作者：
Beatty, Pamela L.;Narayanan, Sowmya;Finn, Olivera J.
慢性炎症与癌症风险增加之间的关系已经得到了很好的证实，但先天免疫和获得性免疫的作用还没有完全阐明。此外，几乎没有考虑到包括癌症抗原在内的慢性炎症相关抗原所起的作用，以及将它们用作疫苗以降低癌症风险的可能性。我们研究了人类肿瘤抗原MUC1，它在结肠癌和导致结肠炎相关结肠癌(CACC)的炎症性肠病(IBD)中异常表达。使用我们新的发展为CACC的MUC1(+)IBD小鼠模型，IL-10基因敲除小鼠与MUC1转基因小鼠杂交，我们证明了针对MUC1的疫苗接种延缓了IBD并防止了进展为CACC。一种机制是诱导MUC1特异性适应性免疫(抗MUC1Ig G和抗MUC1CTL)，似乎可以消除IBD结肠中异常的MUC1(+)细胞。另一个机制是局部和系统微环境的变化。与接种疫苗的小鼠相比，对照组小鼠的IBD以结肠中大量的中性粒细胞和脾中的髓系抑制细胞为主，这可能会损害获得性免疫并促进肿瘤的生长。这表明，慢性炎症的促肿瘤微环境可以通过提高对疾病相关抗原的适应性免疫而转变为肿瘤抑制环境。癌症前传；3(4)；438-46。(C)2010年AACR。
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. Cancer Prev Res; 3(4); 438-46. (C)2010 AACR.