Development of metastatic HER2+ breast cancer is independent of the adaptive immune system
Development of metastatic HER2+ breast cancer is independent of the adaptive immune system
复制标题
DOI：
10.1002/path.2837
复制
发表时间：
2011-05-01
影响因子：
7.3
通讯作者：
de Visser, Karin E.
中科院分区：
文献类型：
--
作者：
Ciampricotti, Metamia;Vrijland, Kim;de Visser, Karin E.
内源性适应性免疫系统的肿瘤调节作用是相当矛盾的。尽管一些临床和实验观察为免疫监视的存在提供了令人信服的证据，但其他研究揭示了适应性免疫系统对原发性癌症发展和转移性疾病的促进作用。我们使用MMTV-NeuT小鼠模型，通过转基因表达活化的HER2/neu癌基因诱导乳腺癌发生，研究了适应性免疫系统作为自发性HER2（+）乳腺肿瘤发生和肺转移形成的调节因子的功能意义。尽管T淋巴细胞和B淋巴细胞浸润人类和实验性HER2（+）乳腺肿瘤，遗传消除适应性免疫系统并不影响癌前增生或原发性乳腺癌的发展。此外，我们证明MMTV-NeuT小鼠肺转移的形成不依赖于适应性免疫系统。因此，我们的研究结果表明，自发的her2驱动的乳腺肿瘤发生和转移形成既不会被免疫监视机制抑制，也不会被改变，也不会被适应性免疫系统促进。版权所有(C) 2011英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
The tumour-modulating effects of the endogenous adaptive immune system are rather paradoxical. Whereas some clinical and experimental observations offer compelling evidence for the existence of immunosurveillance, other studies have revealed promoting effects of the adaptive immune system on primary cancer development and metastatic disease. We examined the functional significance of the adaptive immune system as a regulator of spontaneous HER2(+) breast tumourigenesis and pulmonary metastasis formation, using the MMTV-NeuT mouse model in which mammary carcinogenesis is induced by transgenic expression of the activated HER2/neu oncogene. Although T and B lymphocytes infiltrate human and experimental HER2(+) breast tumours, genetic elimination of the adaptive immune system does not affect development of premalignant hyperplasias or primary breast cancers. In addition, we demonstrate that pulmonary metastasis formation in MMTV-NeuT mice is not dependent on the adaptive immune system. Thus, our findings reveal that spontaneous HER2-driven mammary tumourigenesis and metastasis formation are neither suppressed, nor altered by immunosurveillance mechanisms, nor promoted by the adaptive immune system. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.