CD4+CD25+ regulatory lymphocytes induce regression of intestinal tumors in ApcMin/+ mice
CD4+CD25+ regulatory lymphocytes induce regression of intestinal tumors in ApcMin/+ mice
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DOI：
10.1158/0008-5472.can-04-3104
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发表时间：
2005-05-15
期刊：
影响因子：
11.2
通讯作者：
Schauer, DB
中科院分区：
文献类型：
--
作者：
Erdman, SE;Sohn, JJ;Schauer, DB
人类的结直肠癌是由APC肿瘤抑制基因失活开始的肠上皮细胞的连续遗传变化引起的。宿主免疫在上皮肿瘤发生中的作用知之甚少。先前已经表明，在Rag缺陷小鼠中，CD 4（+）CD 25（+）淋巴细胞抑制结肠炎相关的上皮肿瘤。在这里，我们表明，在Apc（Min/+）小鼠中加入CD 4（+）CD 25（+）淋巴细胞可以减少上皮腺瘤的多样性。白细胞介素-10需要在调节细胞的治疗效果。调节细胞的受体显示肿瘤内的细胞凋亡增加和环氧合酶-2下调与肿瘤消退一致。这些数据表明调节淋巴细胞在肠息肉病Apc（Min/+）小鼠模型中的上皮稳态中的作用。与乳腺癌、前列腺癌、肺癌和其他部位的癌症的相似性提高了调节性淋巴细胞在预防和治疗人类上皮癌中发挥更广泛作用的可能性。
Colorectal cancer in humans results from sequential genetic changes in intestinal epithelia commencing with inactivation of the APC tumor suppressor gene. Roles for host immunity in epithelial tumorigenesis are poorly understood. It has been previously shown that CD4(+)CD25(+) lymphocytes inhibit colitis-associated epithelial tumors in Rag-deficient mice. Here we show that addition of CD4(+)CD25(+) lymphocytes in Apc(Min/+) mice reduces multiplicity of epithelial adenomas. Interleukin-10 was required in regulatory cells for therapeutic effect. Recipients of regulatory cells showed increased apoptosis and down-regulation of cyclooxygenase-2 within tumors coincident with tumor regression. These data suggest a role for regulatory lymphocytes in epithelial homeostasis in the Apc(Min/+) mouse model of intestinal polyposis. Similarities with cancer of the breast, prostate, lung, and other sites raise the possibility of broader roles for regulatory lymphocytes in prevention and treatment of epithelial cancers in humans.