Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hepatology. 2018 Sep;68(3):1025-1041. doi: 10.1002/hep.29904. Epub 2018 Jul 25.
Immune cells constitute an important element of tumor tissue. Accumulating evidence indicates their clinicopathological significance in predicting prognosis and therapeutic efficacy. Nonetheless, the combinations of immune cells forming the immune microenvironment and their association with histological findings remain largely unknown. Moreover, it is unclear which immune cells or immune microenvironments are the most prognostically significant. Here, we comprehensively analyzed the immune microenvironment and its intratumor heterogeneity in 919 regions of 158 hepatocellular carcinomas (HCCs), and the results were compared with the corresponding histological and prognostic data. Consequently, we classified the immune microenvironment of HCC into three distinct immunosubtypes: Immune-high, Immune-mid, and Immune-low. The Immune-high subtype was characterized by increased B-/plasma-cell and T cell infiltration, and the Immune-high subtype and B-cell infiltration were identified as independent positive prognostic factors. Varying degrees of intratumor heterogeneity of the immune microenvironment were observed, some of which reflected the multistep nature of HCC carcinogenesis. However, the predominant pattern of immunosubtype and immune cell infiltration of each tumor was prognostically important. Of note, the Immune-high subtype was associated with poorly differentiated HCC, cytokeratin 19 (CK19) , and/or Sal-like protein 4 (SALL4) high-grade HCC, and Hoshida's S1/Boyault's G2 subclasses. Furthermore, patients with high-grade HCC of the predominant Immune-high subtype had significantly better prognosis. These results provide a rationale for evaluating the immune microenvironment in addition to the usual histological/molecular classification of HCC.
The immune microenvironment of HCC can be classified into three immunosubtypes (Immune-high, Immune-mid, and Immune-low) with additional prognostic impact on histological and molecular classification of HCC. (Hepatology 2018).
免疫细胞是肿瘤组织的重要组成部分。越来越多的证据表明，它们在预测预后和治疗效果方面具有临床病理意义。尽管如此，构成免疫微环境的免疫细胞组合及其与组织学发现的关系在很大程度上仍然未知。此外，目前尚不清楚哪些免疫细胞或免疫微环境对预后意义最大。在这里，我们全面分析了 158 例肝细胞癌（HCC）的 919 个区域的免疫微环境及其肿瘤内异质性，并将结果与相应的组织学和预后数据进行了比较。因此，我们将 HCC 的免疫微环境分为三种不同的免疫亚型：免疫高、免疫中和免疫低。免疫高亚型的特征是 B-/浆细胞和 T 细胞浸润增加，免疫高亚型和 B 细胞浸润被确定为独立的阳性预后因素。观察到免疫微环境的肿瘤内异质性程度不同，其中一些反映了 HCC 癌变的多步骤性质。然而，每个肿瘤的免疫亚型和免疫细胞浸润的主要模式对预后具有重要意义。值得注意的是，免疫高亚型与分化差的 HCC、细胞角蛋白 19（CK19）和/或 Slike 蛋白 4（SALL4）高级别 HCC 以及 Hoshida 的 S1/Boyault 的 G2 亚类相关。此外，主要为免疫高亚型的高级别 HCC 患者的预后明显更好。这些结果为评估免疫微环境提供了依据，除了 HCC 的常规组织学/分子分类之外。
HCC 的免疫微环境可分为三种免疫亚型（免疫高、免疫中和免疫低），对 HCC 的组织学和分子分类具有额外的预后影响。（Hepatology 2018）。
