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单细胞测序揭示肝细胞癌中的免疫抑制景观。

Immunosuppressive landscape in hepatocellular carcinoma revealed by single-cell sequencing.

机构信息

Department of Hepatobiliary Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.

Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin, China.

出版信息

Front Immunol. 2022 Jul 28;13:950536. doi: 10.3389/fimmu.2022.950536. eCollection 2022.

DOI:10.3389/fimmu.2022.950536
PMID:35967424
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9365996/
Abstract

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC), accounting for 75-85% of primary liver cancer cases, is the third leading cause of cancer-related death worldwide. The purpose of this research was to examine the tumor immune microenvironment (TIME) in HCC.

METHODS

We investigated the HCC TIME by integrated analysis of single-cell and bulk-tissue sequencing data to reveal the landscape of major immune cell types.

RESULTS

Regulatory T(Treg) cells were found to be specifically distributed in the TIME of HCC. Several immune checkpoints, including TNFRSF4, TIGIT and CTLA4, were found to be uniquely overexpressed in Treg cells, and the glycolysis/gluconeogenesis pathway was enriched in Treg cells. We also discovered the presence of two NK-cell subsets with different cytotoxic capacities, one in an activated state with antitumor effects and another with an exhausted status. In addition, memory B cells in HCC were found to exist in a unique state, with high proliferation, low differentiation, and low activity, which was induced by overexpression of PRAP1 and activation of the MIF-CD74 axis.

CONCLUSIONS

We revealed the TIME landscape in HCC, highlighting the heterogeneity of major immune cell types and their potential mechanisms in the formation of an immunosuppressive environment. Hence, blocking the formation of the TIME could be a useful therapeutic strategy for HCC.

摘要

背景/目的：肝细胞癌（HCC）占原发性肝癌病例的 75-85%，是全球癌症相关死亡的第三大原因。本研究旨在研究 HCC 的肿瘤免疫微环境（TIME）。

方法

我们通过单细胞和批量组织测序数据的综合分析来研究 HCC 的 TIME，以揭示主要免疫细胞类型的景观。

结果

发现调节性 T（Treg）细胞在 HCC 的 TIME 中特异性分布。几种免疫检查点，包括 TNFRSF4、TIGIT 和 CTLA4，在 Treg 细胞中被发现独特地过表达，并且 Treg 细胞中富含糖酵解/糖异生途径。我们还发现了两种具有不同细胞毒性能力的 NK 细胞亚群，一种处于激活状态具有抗肿瘤作用，另一种处于耗竭状态。此外，发现 HCC 中的记忆 B 细胞存在一种独特的状态，具有高增殖、低分化和低活性，这是由 PRAP1 的过表达和 MIF-CD74 轴的激活诱导的。

结论

我们揭示了 HCC 的 TIME 景观，强调了主要免疫细胞类型的异质性及其在免疫抑制环境形成中的潜在机制。因此，阻断 TIME 的形成可能是治疗 HCC 的一种有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb24/9365996/064cdf305c4a/fimmu-13-950536-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb24/9365996/df6f192431fc/fimmu-13-950536-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb24/9365996/2c00bba3816e/fimmu-13-950536-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb24/9365996/6d1640ed8d47/fimmu-13-950536-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb24/9365996/86a1945596cb/fimmu-13-950536-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb24/9365996/78ed501f0192/fimmu-13-950536-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb24/9365996/064cdf305c4a/fimmu-13-950536-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb24/9365996/df6f192431fc/fimmu-13-950536-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb24/9365996/2c00bba3816e/fimmu-13-950536-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb24/9365996/6d1640ed8d47/fimmu-13-950536-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb24/9365996/86a1945596cb/fimmu-13-950536-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb24/9365996/78ed501f0192/fimmu-13-950536-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb24/9365996/064cdf305c4a/fimmu-13-950536-g006.jpg

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