Suppr超能文献

改良的免疫细胞浸润评分实现了肝细胞癌中 CD8 T 细胞疗效和免疫治疗获益的理想分层。

A modified immune cell infiltration score achieves ideal stratification for CD8 T cell efficacy and immunotherapy benefit in hepatocellular carcinoma.

机构信息

Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China.

Cancer Center of Fujian Medical University, Fujian Medical University Union Hospital, Fuzhou, 350001, China.

出版信息

Cancer Immunol Immunother. 2023 Dec;72(12):4103-4119. doi: 10.1007/s00262-023-03546-9. Epub 2023 Sep 27.

Abstract

Immunotherapy, which aims to enhance the function of T cells, has emerged as a novel therapeutic approach for hepatocellular carcinoma (HCC). Nevertheless, the clinical utility of using flow cytometry to assess immune cell infiltration (ICI) is hindered by its cumbersome procedures, prompting the need for more accessible methods. Here, we acquired gene expression profiles and survival data of HCC from TCGA and GSE10186 datasets. The patients were categorized into two clusters of ICI, and a set of 11 characteristic genes responsible for the differentiation performance of these ICI clusters were identified. Subsequently, we successfully developed a modified ICI score (mICIS) by utilizing the expression levels of these genes. The efficacy of our mICIS was confirmed via mass cytometry, flow cytometry, and immunohistochemistry. Our research indicated that the favorable overall survival (OS) rate could be attributed to the improved function of anti-tumor leukocytes rather than their infiltration. Furthermore, we observed that the low score group exhibited lower expression levels of T-cell exhaustion-associated genes, which was confirmed in both HCC tissues from patients and mice, which demonstrated that the benefits of the low scores were due to enhanced active/cytotoxic CD8 T cells and reduced exhausted CD8 T cells. Additionally, our mICIS stratified the benefits derived from immunotherapies. Lastly, we observed a misalignment between CD8 T-cell infiltration and function in HCC. In summary, our mICIS demonstrated proficiency in assessing the OS rate of HCC and offering significant stratified data pertaining to distinct responses to immunotherapy.

摘要

免疫疗法旨在增强 T 细胞的功能,已成为治疗肝细胞癌 (HCC)的新方法。然而,使用流式细胞术评估免疫细胞浸润 (ICI)的临床应用受到其繁琐程序的限制,需要更易获取的方法。在这里,我们从 TCGA 和 GSE10186 数据集获取 HCC 的基因表达谱和生存数据。将患者分为 ICI 两个亚群,并确定了一组 11 个特征基因,这些基因负责这些 ICI 亚群的分化表现。随后,我们成功地利用这些基因的表达水平开发了改良的 ICI 评分 (mICIS)。通过质谱流式细胞术、流式细胞术和免疫组织化学验证了我们的 mICIS 的功效。我们的研究表明,良好的总生存率 (OS) 归因于抗肿瘤白细胞功能的改善,而不是浸润。此外,我们观察到低评分组 T 细胞耗竭相关基因的表达水平较低,在患者和小鼠的 HCC 组织中得到证实,这表明低评分的益处是由于增强的活跃/细胞毒性 CD8 T 细胞和减少的耗竭 CD8 T 细胞。此外,我们的 mICIS 对免疫治疗的获益进行了分层。最后,我们观察到 HCC 中 CD8 T 细胞浸润和功能之间存在不一致性。总之,我们的 mICIS 能够很好地评估 HCC 的 OS 率,并提供与免疫治疗不同反应相关的重要分层数据。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验