Localization and Density of Immune Cells in the Invasive Margin of Human Colorectal Cancer Liver Metastases Are Prognostic for Response to Chemotherapy
Localization and Density of Immune Cells in the Invasive Margin of Human Colorectal Cancer Liver Metastases Are Prognostic for Response to Chemotherapy
复制标题
DOI：
10.1158/0008-5472.can-11-0268
复制
发表时间：
2011-09-01
期刊：
影响因子：
11.2
通讯作者：
Jaeger, Dirk
中科院分区：
文献类型：
--
作者：
Halama, Niels;Michel, Sara;Jaeger, Dirk
通过原位免疫组化染色对原发性人类结直肠癌（CRC）中肿瘤浸润淋巴细胞（TIL）进行分析，支持了适应性免疫反应影响人类CRC病程这一假说。具体而言，原发性肿瘤中高密度的TIL与良好的预后相关，且与其他预后标志物无关。然而，TIL在转移性CRC病变中的预后作用尚不清楚，它们在对常规化疗的反应或耐药性中的作用也不清楚。我们分析了101个大切片样本中CRC肝转移浸润边缘的TIL密度与化疗反应及无进展生存期之间的关联。利用对完整组织切片的高分辨率自动显微镜技术，客观地得出了CD3、CD8、颗粒酶B或FOXP3阳性免疫细胞的细胞密度。在一个训练集中开发了一种使用TIL密度的预测评分系统，并在一个独立的验证集中成功进行了测试。肝转移浸润边缘的TIL密度能够预测对化疗的反应，敏感性为79%，特异性为100%。高密度值与化疗下更长的无进展生存期之间的关联具有统计学意义。总体而言，这些发现将局部免疫反应对临床病程的影响从原发性肿瘤扩展到了转移性病变。由于对转移性病变中TIL的详细量化揭示了其与化疗疗效和预后的紧密关联，我们建议所开发的评分系统可作为转移性CRC对化疗反应的预测工具。《癌症研究》；71(17)；5670 - 7。（C）2011美国癌症研究协会。
Analysis of tumor-infiltrating lymphocytes (TIL) in primary human colorectal cancer (CRC) by in situ immunohistochemical staining supports the hypothesis that the adaptive immune response influences the course of human CRC. Specifically, high densities of TILs in the primary tumor are associated with good prognosis independent of other prognostic markers. However, the prognostic role of TILs in metastatic CRC lesions is unknown, as is their role in response or resistance to conventional chemotherapy. We analyzed the association of TIL densities at the invasive margin of CRC liver metastases with response to chemotherapy and progression-free survival in a set of 101 large section samples. High-resolution automated microscopy on complete tissue sections was used to objectively generate cell densities for CD3, CD8, granzyme B, or FOXP3 positive immune cells. A predictive scoring system using TIL densities was developed in a training set and tested successfully in an independent validation set. TIL densities at the invasive margin of liver metastases allowed the prediction of response to chemotherapy with a sensitivity of 79% and specificity of 100%. The association of high density values with longer progression-free survival under chemotherapy was statistically significant. Overall, these findings extend the impact of the local immune response on the clinical course from the primary tumor also to metastatic lesions. Because detailed quantification of TILs in metastatic lesions revealed a strong association with chemotherapy efficacy and prognosis, we suggest that the developed scoring system may be used as a predictive tool for response to chemotherapy in metastatic CRC. Cancer Res; 71(17); 5670-7. (C)2011 AACR.