The immune contexture of hepatocellular carcinoma predicts clinical outcome.
The immune contexture of hepatocellular carcinoma predicts clinical outcome.
复制标题
DOI：
10.1038/s41598-018-21937-2
复制
发表时间：
2018-03-29
影响因子：
4.6
通讯作者：
Bockamp E
中科院分区：
文献类型：
--
作者：
Foerster F;Hess M;Gerhold-Ay A;Marquardt JU;Becker D;Galle PR;Schuppan D;Binder H;Bockamp E
免疫系统与癌症发展和治疗的一般相关性越来越被认识到。然而，尽管大多数人类癌症类型的免疫结构已经确定，但缺乏对肝细胞癌（HCC）中免疫肿瘤微环境的整体表征。同样，不同患者亚组之间HCC免疫结构的差异及其对生存率的影响仍有待确定。在这里，我们报告了人类肝癌的免疫结构的计算机分析。使用大型深度测序HCC肿瘤，邻近非肿瘤和健康肝脏高维数据集，我们能够揭示HCC免疫结构中先前未被识别的差异。引人注目的是，我们发现不同的病因和HCC分期与免疫环境的重大变化无关。相反，T细胞和细胞毒性细胞的存在以及巨噬细胞和Th2细胞的缺乏与患者的生存率呈正相关。基于这些新的发现，我们开发了一种预后评分，可以准确区分患者的良好和不良生存期。我们的研究提供了第一个全球性的肝癌免疫结构的特征，并将对未来的肝癌治疗有直接的影响。
The general relevance of the immune system for cancer development and therapy is increasingly recognized. However and although the immune contexture of most human cancer types has been determined, a global characterisation of the immune tumour microenvironment in hepatocellular carcinoma (HCC) is lacking. Equally, differences in the immune contexture of HCC between different patient subgroups and its effect on survival remain to be established. Here we report an in silico analysis of the immune contexture of human HCC. Using large deep sequencing HCC tumour, adjacent non-tumour and healthy liver high-dimensional data sets, we were able to reveal previously unrecognized differences in the immune contexture of HCC. Strikingly, we found that different etiologies and HCC stages were not associated with major changes in the immune contexture. In contrast, the presence of T cells and cytotoxic cells as well as the absence of macrophages and Th2 cells positively correlated with patient survival. Based on these novel findings, we developed a prognostic score that accurately distinguishes between patients with good and poor survival. Our study provides the first global characterisation of the immune contexture of HCC and will have direct implications for future HCC therapies.