新型免疫分类揭示了独特的免疫逃逸机制和基因组改变：对

StephenW

A novel immune classification reveals distinct immune escape mechanism and genomic alterations: implications for immunotherapy in hepatocellular carcinoma

    Zaoqu Liu, Yuyuan Zhang, Chengcheng Shi, Xueliang Zhou, Kaihao Xu, Dechao Jiao, Zhenqiang Sun & Xinwei Han

Journal of Translational Medicine volume 19, Article number: 5 (2021) Cite this article

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Abstract
Background

The tumor immunological microenvironment (TIME) has a prominent impact on prognosis and immunotherapy. However, the heterogeneous TIME and the mechanisms by which TIME affects immunotherapy have not been elucidated in hepatocellular carcinoma (HCC).
Methods

A total of 2195 eligible HCC patients from TCGA and GEO database were collected. We comprehensively explored the different heterogeneous TIME phenotypes and its clinical significance. The potential immune escape mechanisms and what genomic alterations may drive the formation of different phenotypes were further investigated.
Results

We identified three phenotypes in HCC: TIME-1, the “immune-deficiency” phenotype, with immune cell depletion and proliferation; TIME-2, the “immune-suppressed” phenotype, with enrichment of immunosuppressive cells; TIME-3, the “immune-activated phenotype”, with abundant leukocytes infiltration and immune activation. The prognosis and sensitivity to both sorafenib and immunotherapy differed among the three phenotypes. We also underlined the potential immune escape mechanisms: lack of leukocytes and defective tumor antigen presentation capacity in TIME-1, increased immunosuppressive cells in TIME-2, and rich in immunoinhibitory molecules in TIME-3. The different phenotypes also demonstrated specific genomic events: TIME-1 characterized by TP53, CDKN2A, CTNNB1, AXIN1 and FOXD4 alterations; TIME-2 characterized by significant alteration patterns in the PI3K pathway; TIME-3 characterized by ARID1A mutation. Besides, the TIME index (TI) was proposed to quantify TIME infiltration pattern, and it was a superior prognostic and immunotherapy predictor. A pipeline was developed to classify single patient into one of these three subtypes and calculated the TI.
Conclusions

We identified three TIME phenotypes with different clinical outcomes, immune escape mechanisms and genomic alterations in HCC, which could present strategies for improving the efficacy of immunotherapy. TI as a novel prognostic and immunotherapeutic signature that could guide personalized immunotherapy and clinical management of HCC.

StephenW

新型免疫分类揭示了独特的免疫逃逸机制和基因组改变：对肝细胞免疫治疗的意义

    刘枣渠，张玉元，施成成，周学良，徐开好，焦德超，孙振强，韩新伟

转化医学杂志第19卷，文章号：5（2021）引用本文

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抽象
背景

肿瘤免疫微环境（TIME）对预后和免疫治疗有重要影响。然而，在肝细胞癌（HCC）中尚未阐明异质性TIME和TIME影响免疫治疗的机制。
方法

从TCGA和GEO数据库中总共收集了2195名合格的HCC患者。我们全面探讨了不同的异质TIME表型及其临床意义。进一步研究了潜在的免疫逃逸机制以及哪些基因组改变可能驱动不同表型的形成。
结果

我们在肝癌中鉴定出三种表型：TIME-1，即“免疫缺陷”表型，具有免疫细胞耗竭和增殖； TIME-2，“免疫抑制”表型，具有丰富的免疫抑制细胞； TIME-3是“免疫激活的表型”，具有丰富的白细胞浸润和免疫激活作用。三种表型对索拉非尼和免疫疗法的预后和敏感性不同。我们还强调了潜在的免疫逃逸机制：TIME-1中缺乏白细胞和有缺陷的肿瘤抗原呈递能力，TIME-2中免疫抑制细胞增多，并且TIME-3中免疫抑制分子丰富。不同的表型还显示出特定的基因组事件：以TP53，CDKN2A，CTNNB1，AXIN1和FOXD4改变为特征的TIME-1； TIME-2的特征在于PI3K途径中的显着改变模式； TIME-3以ARID1A突变为特征。此外，提出了TIME指数（TI）来量化TIME的浸润模式，它是更好的预后和免疫疗法的预测指标。开发了将单个患者分类为这三种亚型之一的管道，并计算了TI。
结论

我们鉴定了三种具有不同临床结果，免疫逃逸机制和肝癌基因组改变的TIME表型，它们可以为提高免疫疗法的疗效提供策略。 TI作为一种新型的预后和免疫治疗标志，可指导个性化免疫治疗和HCC的临床管理。

StephenW

https://translational-medicine.b ... /s12967-020-02697-y