Cells publishes the latest results of Chinese scientists on the immune micro-environment of liver cancer tumors

June 16, 2017, The Journal of Cell published a research paper entitled "Landscape of inding T cells in liver cancer revealed by single-cell sequencing", the first immunographic map of the microencology of liver cancer at a single-cell level.
immunotherapy is a promising new treatment in recent years, especially immunosuppressant therapy, such as CTLA-4 antibody Ipilimumab and PD-1 antibody pembrolizumab are currently achieving good results. Although this treatment can achieve significant clinical results, the effects are very different between different patients or different types of cancer. The number of DNA mutations, the level of tumor-soaked lymphocytes, and the expression of drug targets all affect the effectiveness of immunotherapy for various types of tumors. Because of the variety of immune cell types and strong heterogeneity involved in tumor development, only by carrying out single-cell level research can we really obtain a systematic and detailed tumor immune map, which can help the development of tumor immunotherapy and the discovery of effective targets and biomarkers.
china has the highest incidence of liver cancer in the world, and the survival rate after surgery is low. Previous studies have shown that liver cancer tissue is rich in tumor-soaked lymphocytes, but there have been few successful immunotherapy treatments for liver cancer compared to the results of immunotherapy on tumors such as melanoma and lung cancer. It is of great significance for the diagnosis and treatment of liver cancer to explore new tumor immunotherapy and find new targets and effective biomarkers by deeply understanding the tumor immune micro-environment of liver cancer.
The Zhang Zemin Research Group of the Biodynatic Optical Imaging Center (BIOPIC) of Peking University, in-depth cooperation with the Research Group of Peng Jirun of Hepatociliary Pancreatic Surgery of the Ninth Clinical Medical College of Peking University and the Ouyang Wenjun Research Group of AMGEN Corporation of the United States, carried out a comprehensive analysis of the transcription group and T-cell subject (TCR) sequence of T lymphocytes in the microenvironment of liver cancer at the single-cell level, and completed a single-cell sequence of more than 5000 T-cells. Based on bio-informational analysis, through sub-group classification, development trajectory analysis and comparison of the distribution of T-cell cloning in different sub-groups, the study explores the relationship between different sub-groups, identifies the specific gene expression of each sub-group, and reveals that T-cells in tumors are very different in function, distribution and development status from T-cells in other parts.
main reasons for the escape of tumors in the immune system include the dysfunction of lethal CD8 T cells and the large presence of inhibitory T cells, and finding targets for these two types of cells is the main direction of immunotherapy. The study focused on exploring the specific expression genes of these two types of cells in tumors, found that the gene Layilin is specific expression in both groups of cells, and proved through in-body experiments that the gene has inhibitory and regulatory effect on the lethal function of CD8 T cells, and may be a new target of immunotherapy.
at the same time, based on TCR data analysis, the study found that liver cancer has a large number of tumor tissue-specific cloning and growth of T cells, but most of these cells are depleted, thus revealing the cause of tumor cell escape immuno surveillance. In addition, the study also depicts the development trajectory of the initial T-cell depletion state, and finds the existence of a class of FOXP3-inhibitory T-cells in the depletion CD8 T-cell sub-group, and suggests the potential development direction that depleted T-cells will further develop into inhibitory T-cells.
this work is the first large-scale single-celled histological study of tumor-related T-cells in the world, providing valuable data resources and laying the foundation for a multi-angle understanding of T-cell characteristics associated with liver cancer. Data accumulation, scientific discovery and theoretical evolution of this work are expected to promote the clinical application of existing immunotherapy programs in liver cancer and to help identify effective targets for immunotherapy for liver cancer, thus accelerating the creation of new liver cancer immunotherapy. At the same time, the work also makes a paradigm for the map of tumor immunity, and provides the basis for similar research and the development of various types of tumor immunity in other tumors in the future.
BIOPIC postdoctoral zheng Chunhong, doctoral student Zhang Yuanyuan, Guo Xinyi, cutting-edge cross-research institute doctoral student Zheng Liangtao, Peking University Medical Department doctoral student Guo Huahu and AMGEN company postdoctoral Ouyang Wenjun are the first authors of the paper. Peng Jirun, Biodynatural Optical Imaging Center of Peking University School of Life Sciences, Beijing Future Gene Diagnostics High-Sharp Innovation Center, Peking University-Tsinghua Life Sciences Joint Center Zhang Zemin, Beijing Century Temple Hospital affiliated with Capital Medical University and Peking University's Ninth Clinical School of Medicine, and Ouyang Wenjun of AMGEN Corporation of the United States were co-authors of the paper. The study was funded by the Beijing Future Genetic Diagnostics High-Sophisticated Innovation Center, the National Key Research and Development Program, the National Natural Science Foundation of China, and the Peking University-Tsinghua Joint Center for Life Sciences. (Source: Science Network)
paper Information: