Institute of Translational Immunology and Research Centre for Immunotherapy, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.
First Department of Medicine, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.
Sci Rep. 2018 Mar 29;8(1):5351. doi: 10.1038/s41598-018-21937-2.
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.
免疫系统对癌症的发生和治疗具有普遍意义,这一点已越来越受到重视。然而,尽管大多数人类癌症类型的免疫结构已经确定,但肝癌(HCC)的肿瘤免疫微环境的全面特征尚不清楚。同样,不同患者亚组中 HCC 的免疫结构差异及其对生存的影响也有待确定。在这里,我们报告了对人类 HCC 免疫结构的计算机分析。使用大型 HCC 肿瘤、相邻非肿瘤和健康肝脏的高通量测序数据集,我们能够揭示 HCC 免疫结构以前未被识别的差异。引人注目的是,我们发现不同的病因和 HCC 分期与免疫结构的重大变化无关。相比之下,T 细胞和细胞毒性细胞的存在以及巨噬细胞和 Th2 细胞的缺失与患者的生存呈正相关。基于这些新发现,我们开发了一种预后评分,能够准确区分生存良好和不良的患者。我们的研究首次对 HCC 的免疫结构进行了全面描述,这将对未来的 HCC 治疗产生直接影响。