The tumor area occupied by Tbet+ cells in deeply invading cervical cancer predicts clinical outcome.
The tumor area occupied by Tbet+ cells in deeply invading cervical cancer predicts clinical outcome.
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DOI：
10.1186/s12967-015-0664-0
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发表时间：
2015-09-10
影响因子：
7.4
通讯作者：
van der Burg SH
中科院分区：
文献类型：
--
作者：
Gorter A;Prins F;van Diepen M;Punt S;van der Burg SH
原发性宫颈癌对周围正常组织的深度浸润是术后放疗和相对较差生存率的预后参数。然而，在手术时血液中具有肿瘤特异性免疫的患者显示出更好的无病生存期。在这里，我们分析了这是否是由于肿瘤中更多的肿瘤排斥免疫群体。通过免疫组织化学染色，对58例浸润深部正常组织的宫颈肿瘤患者的肿瘤切片进行免疫细胞（CD 45）、IFNγ产生细胞（Tbet）和调节性T细胞（Foxp 3）的染色。扫描载玻片，并使用计算机软件客观定量肿瘤面积和不同染色的免疫细胞的浸润。我们发现CD 45+细胞占据肿瘤的百分比增加与Tbet+细胞和Foxp 3+细胞的肿瘤浸润增强密切相关。此外，除了患者的淋巴结状态外，肿瘤内CD 45+免疫细胞、Tbet+细胞而非Foxp 3+细胞占据的区域与较长的无病生存期和疾病特异性生存期相关。此外，这些免疫参数和淋巴结状态之间的相互作用分析表明，肿瘤浸润Tbet+细胞的独立预后影响。这在多变量考克斯分析中得到证实。由优先I型定向的CD 45+细胞浸润占据的区域形成了患者淋巴结状态之上的无复发和疾病特异性生存的独立预后因素。本文的在线版本（doi：10.1186/s12967-015-0664-0）包含补充材料，可供授权用户使用。
Deep invasion of the normal surrounding tissue by primary cervical cancers is a prognostic parameter for postoperative radiotherapy and relatively worse survival. However, patients with tumor-specific immunity in the blood at the time of surgery displayed a much better disease free survival. Here we analyzed if this was due to a more tumor-rejecting immune population in the tumor. Tumor sections from a group of 58 patients with deep normal tissue-invading cervical tumors were stained for the presence of immune cells (CD45), IFNγ-producing cells (Tbet) and regulatory T cells (Foxp3) by immunohistochemistry. The slides were scanned and both the tumor area and the infiltration of the differently stained immune cells were objectively quantified using computer software. We found that an increased percentage of tumor occupied by CD45+ cells was strongly associated with an enhanced tumor-infiltration by Tbet+ cells and Foxp3+ cells. Furthermore, the area occupied by CD45+ immune cells, Tbet+ cells but not Foxp3+ cells within the tumor were, in addition to the lymph node status of patients, associated with a longer disease free survival and disease specific survival. Moreover, interaction analyses between these immune parameters and lymph node status indicated an independent prognostic effect of tumor infiltrating Tbet+ cells. This was confirmed in a multivariate Cox analysis. The area occupied by a preferentially type I oriented CD45+ cell infiltrate forms an independent prognostic factor for recurrence-free and disease-specific survival on top of the patient’s lymph node status. The online version of this article (doi:10.1186/s12967-015-0664-0) contains supplementary material, which is available to authorized users.