Evolving immunosuppressive microenvironment during human cervical carcinogenesis
Evolving immunosuppressive microenvironment during human cervical carcinogenesis
复制标题
人类宫颈癌发生过程中不断演变的免疫抑制微环境
DOI：
10.1038/mi.2008.33
复制
发表时间：
2008-09-01
影响因子：
8
通讯作者：
Smith-McCune, K.
中科院分区：
文献类型：
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作者：
Kobayashi, A.;Weinberg, V.;Smith-McCune, K.
人乳头瘤病毒（HPV）感染可导致宫颈癌。为了了解HPV如何逃避免疫根除，我们检查了人类正常宫颈、宫颈上皮内瘤变（CIN）和癌症中免疫细胞的生物表型。免疫荧光和免疫组化检测叉头盒蛋白-3（FOXP 3）、吲哚胺2，3-双加氧酶（IDO）、白细胞介素（IL）-10和干扰素（IFN）-γ的表达和细胞定位。间质FOXP 3+细胞、IDO+细胞、IL-10+细胞、CD 1a+细胞和巨噬细胞的平均细胞密度从正常子宫颈到癌症显著增加，而IFN-γ +和MMP-9+细胞的密度从正常子宫颈到CIN增加，但在癌症中降低。流式细胞术证实，与正常宫颈相比，CIN中表达IFN-γ和转化生长因子-β的宫颈T细胞显著升高。在激活后，CIN中表达IFN-γ的宫颈T细胞的比例比正常人显著增加。一个独特的子集的形态不成熟的间质树突状细胞表达IL-10和IDO是更多的癌症比正常宫颈和CIN。宫颈内潜在的抑制性免疫环境可能允许HPV相关的宫颈癌发生。
Chronic infection with human papillomavirus (HPV) can result in cervical cancer. To understand how HPV escapes immune eradication, we examined biophenotypes of immune cells in human normal cervix, cervical intraepithelial neoplasia (CIN), and cancer. Expression and cellular localization of Forkhead box protein-3 (FOXP3), indolamine 2,3-dioxygenase (IDO), interleukin (IL)-10, and interferon (IFN)-gamma were examined by immunofluorescence and immunohistochemistry. Mean cell densities of stromal FOXP3+ cells, IDO+ cells, IL-10+ cells, CD1a+ cells, and macrophages significantly increased from normal cervix to cancer, whereas densities of IFN-gamma+ and MMP-9+ cells increased from normal cervix to CIN but decreased in cancer. Flow cytometry confirmed significant elevation of cervical T cells expressing IFN-gamma and transforming growth factor-beta in CIN compared with normal cervix. Upon activation, a significantly increased proportion of cervical T cells expressed IFN-gamma in CIN than normal. A unique subset of morphologically immature stromal dendritic cells expressing IL-10 and IDO was more numerous in cancer than in normal cervix and CIN. The potentially suppressive immune milieu in the cervix may be permissive of HPV-associated cervical carcinogenesis.