Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma.
Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma.
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DOI：
10.1038/s41467-021-24010-1
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发表时间：
2021-06-17
影响因子：
16.6
通讯作者：
Ng IO
中科院分区：
文献类型：
--
作者：
Ho DW;Tsui YM;Chan LK;Sze KM;Zhang X;Cheu JW;Chiu YT;Lee JM;Chan AC;Cheung ET;Yau DT;Chia NH;Lo IL;Sham PC;Cheung TT;Wong CC;Ng IO
肿瘤微环境中肿瘤细胞和免疫细胞之间的相互作用在癌症发展中很重要。免疫细胞与肿瘤细胞相互作用来塑造这个过程。在这里，我们使用单细胞RNA测序分析来描述HBV相关的人肝细胞癌（HCC）患者队列中的免疫景观和肿瘤异质性。我们发现肿瘤相关巨噬细胞抑制肿瘤T细胞浸润，并且TIGIT-NECTIN 2相互作用调节免疫抑制环境。免疫细胞向更免疫抑制和耗尽状态的细胞状态转变证实了整体促癌免疫细胞景观。此外，整体分子谱的异质性揭示了肿瘤内和肿瘤间异质性的共存，但在后者中更明显。这种免疫抑制景观和细胞间相互作用的分析提供了机制信息的设计有效的免疫肿瘤治疗肝细胞癌。HBV相关的人肝细胞癌（HCC）中肿瘤微环境的不同细胞相互作用以促进肿瘤免疫。在这里，作者使用单细胞RNA测序来鉴定TIGIT-NECTIN 2作为肿瘤相关巨噬细胞减少肿瘤内T细胞活化的途径。
Interaction between tumor cells and immune cells in the tumor microenvironment is important in cancer development. Immune cells interact with the tumor cells to shape this process. Here, we use single-cell RNA sequencing analysis to delineate the immune landscape and tumor heterogeneity in a cohort of patients with HBV-associated human hepatocellular carcinoma (HCC). We found that tumor-associated macrophages suppress tumor T cell infiltration and TIGIT-NECTIN2 interaction regulates the immunosuppressive environment. The cell state transition of immune cells towards a more immunosuppressive and exhaustive status exemplifies the overall cancer-promoting immunocellular landscape. Furthermore, the heterogeneity of global molecular profiles reveals co-existence of intra-tumoral and inter-tumoral heterogeneity, but is more apparent in the latter. This analysis of the immunosuppressive landscape and intercellular interactions provides mechanistic information for the design of efficacious immune-oncology treatments in hepatocellular carcinoma. Different cells of the tumour microenvironment in HBV-associated human hepatocellular carcinoma (HCC) interact to promote tumour immunity. Here the authors use single cell RNA sequencing to identify TIGIT-NECTIN2 as a pathway by which tumour-associated macrophages reduce intratumour T cell activation.
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