My scientist first revealed the liver cancer immune map for the first time.
June 27, 2017 Source: Guangming Daily
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Recently, Chinese scientists have sequenced more than 5,000 T cells from multiple liver cancer patients, thus delineating the gene expression profile of each cell. This is the first time in the world that T cells in cancer patients are at the single cell level. Conducting such a large-scale detailed analysis lays the foundation for the discovery of immunotherapy for liver cancer and other cancers in the future.
This is led by Professor Zhang Zemin from the BIOPIC Center of Peking University School of Life Sciences, Professor Peking University-Tsinghua Life Science Joint Center, Beijing Century University Hospital of Capital Medical University and Professor Peng Jirun, Director of Hepatobiliary and Pancreatic Surgery, Peking University Ninth Clinical Medical College, and Amgen ( AMGEN) Dr. Ouyang Wenjun's research results have been published in the international journal Cell, and this reporter interviewed Peng Jirun exclusively.
Discover potential targets for anti-tumor drug development
"There are countless new cells born every day in the human body. Some may be abnormal in genetics and performance, and have a tendency to malignant. T cells, as immune cells present in the lymphatic system of the human body, can monitor and attack these 'inners'. Kill them in time.†Peng Jirun said that despite this, tumor cells can try to escape monitoring. This phenomenon is called immune escape, which is the reason why tumor cells can avoid attacks and proliferate. Therefore, to understand the principle of tumor cell dodge attack, it is possible to develop drugs to "activate" T cells and let them kill tumor cells.
Peng Jirun introduced that the dysfunction of T cells and the large number of inhibitory T cells are important reasons for tumor cells to evade human immune surveillance. The search for therapeutic targets for these two types of cells is the main direction of immunotherapy. "Through a certain role, tumor cells may cause T cells to prematurely 'age', or lose the 'bullet' of the attack, and may even be 'rebelled', and inhibit other types." Peng Jirun said that the study found liver cancer. There are a large number of premature "aging" killer T cells in the tissue, and suppressive T cells are found in this type of T cells, from which it can be inferred that normal T cells will first become "aged", and then It has the ability to inhibit other similar functions, which depicts the specific process by which tumor cells evade immunity.
In this study, a gene called Layilin was also found to be abnormally expressed in "aging" killer T cells and suppressor T cells. In vitro experiments also demonstrated that the abnormal expression of this gene inhibits T cell regulation. Role, therefore "Layilin gene may become a new target for immunotherapy." Peng Jirun said that this means that through the study of the mechanism of action between tumor cells and this target, it may be possible to develop new anticancer drugs that act on this target in the future.
Providing new possibilities for treating liver cancer
"More than 20 years ago, people discovered that there is a target of programmed death receptor-1 (PD-1) on T cells, and now the anticancer drugs that target this target have saved the lives of many cancer patients." Peng Jirun said "PD-1 is like a 'brake' on T cells. Tumor cells can pull 'brakes', so that T cells 'brake' and no longer attack tumor cells."
Anticancer drugs developed according to this principle have yielded significant results in the treatment of malignant melanoma and lung cancer. "This drug is equivalent to a layer of protective device on the PD-1, so that the tumor cells can not pull the 'brake', T cells will attack normally." Peng Jirun said. However, due to factors such as the number of DNA mutations, the level of viable lymphocytes inside the tumor, and the expression of drug targets, the effect of this drug on different patients and different cancers is very uneven. For example, it has no significant effect on most liver cancer patients and about 1/3 of lung cancer patients. This requires further detailed study of single-cell levels, the discovery of more interactions between lymphocytes and tumor cells in humans, and the exploration of more pathways for the development of new anti-cancer drugs.
He introduced the research results published in "Cell", which performed single cell analysis on the blood of liver cancer patients, the surrounding tumors, the junction of tumors and normal tissues, and more than 5,000 T cells extracted from tumors. "This is an emerging life science analysis method. By analyzing the DNA, RNA and the molecular properties of many molecules on each cell, we can find the target for treating tumors. This time, we analyzed the T cells on tumor immunity. The molecular group and other bioactive markers are the most basic life science level exploration for the development of new drugs," said Peng Jirun.
"In addition to the Layilin gene, the database formed in this database contains a lot of target information, so this is a veritable 'treasure house'." Peng Jirun said that the discovery of more targets means that it is possible to develop a new type of anti-cancer. Drugs save more lives.
Providing data "treasures" for scientists around the world
Although single-cell analysis is very effective, it takes a lot of time and effort because of the large amount of genetic and biological information contained in each cell. This is why the immune cells in tumor patients have never been done before. One of the reasons for extensive and detailed research. This study took three years to complete the analysis of such a large number of immune cells using the single cell analysis method for the first time in the world, and revealed the detailed immunological map of liver cancer for the first time, and constructed a massive amount of human immune cell gene expression in liver cancer patients. database.
For this study, an anonymous reviewer from the Cell Journal said in an opinion that “it must be published as soon as possible because the data is too valuable.â€
"If the information about immune cells related to liver cancer is likened to a thick book, then what we are facing now is the pieces torn from this book. Each piece contains information, and this time the institute The amount of information obtained is just as large as the number of these fragments. It is a massive database that cannot be measured.†In Peng Jirun’s view, this database contains a large number of “passwords†that resolve humans’ fight against cancer, requiring scientists to step through and decode them step by step. .
Currently, the database is open to the world and is available to interested research colleagues. “Maybe someone will find information useful for treating cancer and develop new anti-tumor drugs.†Peng Jirun said, “We opened the door to the 'treasure house' for everyone and took out one or two eye-catching treasures. And what treasures are there, and continue to 'explore' and 'check out'." (Reporter Zhan Yuan)
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