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The immune landscape and dynamics characterization of liver cancer by single-cell RNA sequencing

时间:2019/11/01   放大字体 放小字体 打印

Liver cancer, including hepatocellular carcinoma, is the third leading cause of cancer-related mortality in the world, with the highest incidence in China. Chronic infection of HBV is the main cause of hepatocellular carcinoma (HCC), and the infection often causes chronic inflammation in the tumor microenvironment (TME). Immune escape is considered to be one of the signs of cancer development. Current research has indicated multiple immune escape mechanisms in tumors, and the importance of characterizing various immune cells in the TME. Single-cell RNA sequencing (scRNA-seq) technologies are powerful tools for studying the landscape and dynamics of different types of immune cells.

 

On October 31, 2019, a collaborative study from three research groups (Zemin Zhang’s group from the Biomedical Pioneering Innovation Center, Peking University; Jirun Peng’s group from Beijing Shijitan Hospital and the Cancer Immunology and Immune Modulation group from Boehringer-Ingelheim) was published in Cell, entitled “Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma”. The authors combined 10x Genomics and SMART-seq2 scRNA-seq technologies to systematically characterize the immune cells from multiple tissues of liver cancer patients. They also illustrated the dynamic migration and state transition processes of these immune cells, and explored their application potential in the treatment of liver cancer.

The researchers integrated 10x Genomics and full-length SMART-seq2 scRNA-seq technologies, and isolated CD45+ immune cells from liver tumors, adjacent liver tissues, hepatic lymph nodes (LNs), blood, and ascites of HCC patients, and generated the transcriptome data at the single cell level. They then analyzed the data from several different perspectives. First, the researchers evaluated the two different sequencing technologies and downstream analyses methods, and found that integrating the two types of data provided unique insight into the immune cell transcriptomes. Therefore, the combination of different scRNA-seq techniques may represent a new paradigm for cell heterogeneity research. Second, they observed a dendritic cell (DC) population highly expressing LAMP3 both in vitro and in vivo, which might reflect an activated and mature state. Based on different bioinformatics analyses, this population was observed to have capacity to migrate from tumors to LNs, and interact with lymphocytes by expressing different ligands/receptors. Further, by expression similarity analysis, the researchers found that macrophages in tumors exhibited different transcriptional states and ability to egress to ascites. Finally, they found that myeloid cells and lymphocytes in ascites are mainly derived from tumors and blood, respectively, but proliferating T cells in tumors often accumulated in ascites.

In this study, the researchers collected multiple autologous tissues, including the ascites of HCC patients, to characterize the immune cells in this important pathological site for the first time. Such study design gave them the opportunity to not only describe the immune components and states of the TME, but also depict the dynamics of tumor-infiltrating immune cells across tissues. Therefore, the study sheds new light on the immune landscape and dynamics of HCC, and holds potential relevance for other cancer indications.