为肝细胞癌武装 GPC3 CAR-T 细胞：多少才足够，下一步是什么？
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
单细胞测序揭示的肝细胞癌免疫抑制景观
英文原题：Immunosuppressive landscape in hepatocellular carcinoma revealed by single-cell sequencing.
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Immunosuppressive landscape in hepatocellular carcinoma revealed by single-cell sequencing.
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研究概要
我们揭示了 HCC 中的 TIME 景观，突出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 HCC 的一种有用治疗策略。
研究思路结论见上方概要
背景
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。本研究旨在探讨HCC的肿瘤免疫微环境（TIME）。
方法
我们通过整合分析单细胞和 bulk 组织测序数据，研究了 HCC TIME，以揭示主要免疫细胞类型的图谱。
结果
调节性T（Treg）细胞被发现特异性分布于HCC的TIME中。包括TNFRSF4、TIGIT和CTLA4在内的多个免疫检查点被发现仅在Treg细胞中过表达，且糖酵解/糖异生通路在Treg细胞中富集。我们还发现存在两种具有不同细胞毒能力的NK细胞亚群，一种处于具有抗肿瘤效应的活化状态，另一种处于耗竭状态。此外，HCC中的记忆B细胞被发现处于一种独特状态，具有高增殖、低分化和低活性，这是由PRAP1过表达和MIF-CD74轴的激活所诱导的。
展开英文摘要原文
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.
论文信息
- 作者
- Bai Y、Chen D、Cheng C、Li Z、Chi H、Zhang Y、Zhang X、Tang S
- 单位
- Department of Hepatobiliary Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Frontiers in immunology2022
- 原文标识
- PubMed 35967424 · DOI 10.3389/fimmu.2022.950536
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