Correlation of CXCL12 Expression and FoxP3+ Cell Infiltration with Human Papillomavirus Infection and Clinicopathological Progression of Cervical Cancer
Correlation of CXCL12 Expression and FoxP3+ Cell Infiltration with Human Papillomavirus Infection and Clinicopathological Progression of Cervical Cancer
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DOI：
10.2353/ajpath.2009.090295
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发表时间：
2009-10-01
影响因子：
6
通讯作者：
Poznansky, Mark C.
中科院分区：
文献类型：
--
作者：
Jaafar, Fatimah;Righi, Elda;Poznansky, Mark C.
人宫颈癌是一种具有明确的组织病理学和临床进展模式的免疫原性肿瘤。肿瘤浸润性T细胞参与肿瘤的免疫控制；然而，宫颈癌通过其与人乳头瘤病毒（HPV）感染的关联以及通过产生细胞因子和趋化因子来失调这种免疫反应。动物肿瘤模型揭示了趋化因子基质细胞衍生因子-1 （SDF-1或CXCL12）的过量产生与肿瘤特异性免疫调节失调之间的关联。因此，我们提出CXCL12在宫颈癌前病变和癌性病变中的表达与组织病理学进展、肿瘤免疫控制丧失和HPV感染相关。我们发现，在鳞状和腺状病变中，癌症分期与CXCL12表达以及肿瘤病变的HPV16+（高风险）状态之间存在显著关联。肿瘤进展与肿瘤中FoxP3 t细胞浸润水平的增加有关。FoxP3和CXCL12在鳞状和腺状肿瘤中的表达显著相关。酶联免疫吸附试验和Western blotting支持了这些观察结果。此外，我们在ThinPrep宫颈涂片中证实了CXCL12在核异常细胞中的表达。本研究明确了CXCL12表达和FoxP3（+）细胞浸润与HPV感染和宫颈癌进展之间的关系。它支持在宫颈涂片和活检中检测CXCL12作为该疾病的额外生物标志物。（美国病理杂志2009,175:1525-1535;DOI: 10.2353/ajpath.2009.090295）
Human cervical cancer is an immunogenic tumor with a defined pattern of histopathological and clinical progression. Tumor-infiltrating T cells contribute to immune control of this tumor; however, cervical cancer dysregulates this immune response both through its association with human papillomavirus (HPV) infection and by producing cytokines and chemokines. Animal tumor models have revealed associations between overproduction of the chemokine stromal cell-derived factor-1 (SDF-1 or CXCL12) and dys-regulation of tumor-specific immunity. We therefore proposed that CXCL12 expression by cervical precancerous and cancerous lesions correlates with histopathological progression, loss of immune control of the tumor, and HPV infection. We found a significant association between cancer stage and CXCL12 expression for squamous and glandular lesions as well as with the HPV16+ (high-risk) status of the neoplastic lesions. Cancer progression was correlated with increasing levels of FoxP3 T-cell infiltration in the tumor. FoxP3 and CXCL12 expression significantly correlated for squamous and glandular neoplastic lesions. These observations were supported by enzyme-linked immunosorbent assay and Western blotting. In addition, we demonstrated CXCL12 expression by dyskaryotic cells in ThinPrep cervical smears. This study robustly links increased CXCL12 expression and FoxP3(+)-cell infiltration to HPV infection and progression of cervical cancer. It supports the detection of CXCL12 in cervical smears and biopsies as an additional biomarker for this disease. (Am J Pathol 2009, 175:1525-1535; DOI: 10.2353/ajpath.2009.090295)