"Turn" visit to Fudan University Zhongshan Hospital Professor Wu Dojiao: single-cell sequencing technology for the field of immune metabolism has brought new opportunities and challenges.

Click on the top of translational medicine network to subscribe to our dry goods reliable practical Zhuan interview is a brand interview column of translational medicine network, a platform for intelligent exchange and collision among experts, big men and well-known enterprises, and an important force to promote the healthy development of the industry. The interview of Zhuan is aimed at creating the most famous expert interview column in the field of translational medicine.on July 9, the salon on Application of single cell sequencing technology was held in Zhangjiang · China Pharmaceutical Valley Biomedical Innovation exchange center. The conference focused on the theme of "Application of single cell sequencing technology", and attracted more than 80 experts, entrepreneurs and practitioners involved in the conference, and the venue was full of seats.the atmosphere of the whole process was hot, and the conference was successfully concluded with the smooth development of the academic forum.after the conference, I had an in-depth interview with Professor Wu Duojiao, the Clinical Medicine Research Institute of Zhongshan Hospital Affiliated to Fudan University, and asked her to introduce the research related to immune metabolism and the application and development of single cell sequencing.in the interview, Professor Wu talked about his own research experience and expressed his unique opinions from the clinical point of view.question 1, Professor Wu, thank you for taking the time out of your busy schedule to accept this interview.we understand that you completed your postdoctoral research in the Department of immunology, Washington University, St. Louis, USA. can you give us a brief introduction to your research content at that time? What effect did this have on your later research? Yes, I did postdoctoral research in the United States. At that time, I read about the frontier progress of immune metabolism in China. I thought that this direction was not only new but also very important, so I applied to the Department of immunology of Washington University in St. Louis. Br / >at that time, the molecular mechanism of interferon reactivation was about the immune function of type I cells.this study deepens our understanding of immune regulation mechanism of infection from the perspective of metabolism, and provides a new idea of anti-virus infection.for me, my postdoctoral experience has enabled me to learn the research techniques and methods of immune metabolism, as well as the frontier progress, so as to lay a foundation for my work after returning home.Q2. We understand that the regulatory mechanism of immune metabolism and intervention targets are your research focus.can you talk to us about how the research on the regulation mechanism of immune metabolism plays a role in tumor treatment? What are the recent advances in tumor immunotherapy? In recent years, it has been recognized that cellular metabolizing reprogramming is the basis for immune cells to perform specific functions and is one of the important mechanisms for regulating the innate and adaptive immune response of the body.for all kinds of organisms, the immune system continuously senses and responds to the threat of the external environment, which is a huge energy demand and consumption process.for example, immune cells secrete a large number of cytokines, chemokines and inflammatory mediators after activation; these immune responses depend on the rapid absorption and utilization of nutrients by immune cells from the microenvironment.the complexity and diversity of tumor immune microenvironment are the key factors affecting the effect of immunotherapy.for example, the uptake of nutrients by tumor cells in the tissue microenvironment competitively inhibits the metabolism and function of tissue infiltrating T cells.immunometabolism research is to discover the metabolic mechanism of immune cell function regulation in tumor. By clarifying these mechanisms, we can find new targets and enhance the anti-tumor function of immune cells through targeted metabolism. cytotoxic CD8 + T cells are the key cells of tumor specific adaptive immune response; previous studies on the metabolism of CD8 + T cells mostly focused on glycolysis. With the deepening of the research, new evidence suggests that CD8 + T cells may have more complex metabolic patterns, which are closely related to their tumor killing function. the research work of my research group mainly focuses on finding the metabolic mechanism that affects the function of CD8 + T cells in tumor or infection. it is a new challenge and opportunity in the field of cancer treatment to precisely reactivate immune cell function by targeting metabolism. Q3. You have done a study on fat metabolism of immune cells and tumor immunity. Why do you want to study the metabolism of cellular fat? Are there any difficulties and breakthroughs? Whether innate immune cells or adaptive immune cells such as teff, Treg and TM, they exist in tissues and continuously sense the external environment, initiate antigen-specific immune response or immune tolerance response. fatty acid oxidation plays a key role in regulating innate and adaptive immune responses. the dominant role of aerobic glycolysis can be observed in inflammatory and rapidly proliferating immune cells, while many non-inflammatory and rapidly proliferating immune cells show a dependence on fatty acid oxidation, which is related to cell survival time, including M2 macrophages, Treg cells and memory T cells. Why do fatty acid synthesis and oxidation have opposite immunoregulatory functions? It's not clear. does this depend on whether the primary needs of different immune cells are different, whether ATP is produced efficiently or a large number of metabolic intermediates are produced for biosynthesis? One possibility is that effector immune cells actively absorb peripheral nutrients and produce abundant metabolic intermediates, such as acetyl coenzyme A, which are used for biosynthesis. however, tolerance cells such as M2 macrophages or Treg cells mostly live in the tissue microenvironment where nutrients are relatively deficient, so the efficiency of ATP production is very important. for tolerant cells, it is more important to produce more ATP through fatty acid oxidation and to maintain normal mitochondrial function. another possibility is that effector cells need lipids formed by fatty acid synthesis to construct cell membrane during rapid growth and proliferation, while memory immune cells grow slowly and require less biosynthesis, so they are mainly catabolized. the focus of my research group is to study the effects of fatty acid metabolism on the development, differentiation and function of immune cells, The series of articles published by clinical and translational medicine discussed the metabolic heterogeneity of infiltrating depleted CD8 + T cells in hepatocellular carcinoma, and the relationship between fatty acid metabolism and cell function. at present, the understanding of the impact of metabolic substrates and pathways on immune cells is still very limited, and more evidence and in vivo experiments are needed to confirm. The problem is the limitations of research methods or technologies. For example, it is still unable to monitor the real-time changes of cell metabolism in vivo. Q4. As the Secretary General of gene detection technology branch of China Medical Biotechnology Association, can you briefly introduce the specific application of gene detection, especially single cell sequencing technology? Is there any bottleneck? A single cell sequencing technology has been very mature at present, but the clinical transformation application is still in its infancy. at present, the application of assisted reproduction is at the forefront of comparison, and the fields of tumor, immunity, stem cells and other fields also have great growth potential. in addition, the application of single cell technology in drug target screening and validation, diagnosis and concomitant diagnosis development is still in the early stage, but it has great application potential. first of all, there must be clear evidence of clinical benefits in order to affect the clinical application of single cell sequencing technology. In addition, factors such as technology iteration, cost control, R & D investment and collaborative integration of the whole industry chain will also affect the transformation speed. Q5. How do you share your feelings in your research career? My deepest feeling is that starting from clinical problems, such research has vitality and is easy to obtain. Q6. With the rapid development of single cell sequencing technology, what impact do you think the single cell sequencing will bring to the research of cellular immune metabolism and what is the future prospect? What are your expectations for the development of clinical transformation application of single cell sequencing? The development of immunometabolism is closely related to technological progress. For example, highly sensitive metabonomics methods enable us to accurately detect the changes of metabolites during the activation of immune cells, and then analyze the relationship between metabolism and immune cell effector function. the immune system is extremely complex, and the metabolic changes are also changing rapidly. the commonly used markers do not fully describe the diversity of immune types, and cell identity is highly plastic (depending on tissue and environment). using single cell sequencing can help us find new cell subsets and corresponding metabolic characteristics, whether common or specific, and deepen our understanding of the regulatory mechanism of immune metabolism in diseases. so as to identify new biomarkers, develop more relevant animal models, predict drug reactions, and identify new cell targets and pathways, thus bringing new immunotherapy with less harm and higher efficiency. 12 Professor Wu Duojiao, M.D. and master supervisor of the school of clinical medicine, Zhongshan Hospital Affiliated to Fudan University, director of the office of the Institute of clinical medicine, Zhongshan Hospital Affiliated to Fudan University, deputy director of oncogene diagnosis and biotherapy center of Jinshan Hospital, Fudan University, and deputy director of Shanghai Artificial Intelligence Engineering Technology Research Center for cardiopulmonary diseases. supported by "Shanghai Youth Science and technology star" and "Shanghai Pujiang talents" program. focusing on the research of immune metabolism regulation mechanism and intervention targets; in recent five years, as the first author or corresponding author, he has published more than 40 papers in SCI journals such as immunity, Semin cancer Biol., Journal for immunotherapy of cancer, and edited or participated in the compilation of 5 English Monographs in the fields of immune metabolism and systemic immunology. served as the Secretary General of gene detection technology branch of China Medical Biotechnology Association and vice chairman of youth committee, member of translational medicine special committee of Chinese society of clinical oncology.