癌症免疫疗法 z-bo 2020-10-16 435

　　Scientists at the University of California and other institutions have discovered through research that cancer immunotherapy can be specifically suppressed by liver tumors. Cancer immunotherapy has become a very promising standard treatment for many different cancers. It can be cured in some cases, but it is not effective for everyone. People are gradually paying attention to understanding the reasons.

　　For example, clinicians say that when cancer starts to metastasize from the primary site and form a secondary tumor in the liver, cancer patients who initially respond well to immunotherapeutics (such as checkpoint inhibitors) will receive these treatments. , Resistance to checkpoint inhibitors (such as drugs that target PD-1); in this study, the researchers used a special mouse model to study the resistance of cancer patients to treatment. Molecular mechanism. Researchers have found that adding a second checkpoint inhibitor to the combination therapy may help overcome the resistance of cancer cells to liver metastasis and the effectiveness of immunotherapy.

　　Dr. Li said that the liver actually causes differences between distant immune cells, and more importantly, the liver chooses enemies that it wants or does not want to protect. Cancer cells can trick the host's immune system to avoid detection. It produces a lot of proteins, such as PD-L1, which shuts down cells called regulatory T cells (Tregs) and weakens the ability of other T cells to attack cancer. ability. Some checkpoint inhibitors neutralize this hidden process by preventing the collection of PD-L1 and PD-1 shutdown switches in T cells, so that the body has normal protective immunity against cancer cells. Prompt to generate a response. The role of the liver is to directly filter out most of the blood in the digestive system and other parts of the body, and it plays a very important role in regulating the function of the host's immune system. In this article, the scientists stimulated cancer metastasis in mice by implanting cancer cells in two different locations, first under the skin, and then in the liver or lungs. The results of the study show that when cancers colonize the liver, they have special suppressive properties. In other words, cells can use the potential of the liver to retrain the host's immune system and influence the immune response of distantly related cancers. Compared with mice transplanted with secondary cancer cells in the lungs, after anti-PD-1 treatment, the survival rate of mice with secondary liver cancer was significantly reduced, and the immune system did not learn cognition. No liver tumors have been found, especially those related to subcutaneous transplantation in mice. This resolution of the immune system may provide researchers with some clues. Regardless of whether liver tumors change Tregs or change the response of other T cells to a single related tumor, only a few types of cells can specifically regulate the host's immune system, including Tregs.

　　Through single-cell analysis, the researchers found that in mice with liver tumors, the T cells associated with the primary tumor may not be highly activated, causing liver tumors to change the expression of genes in Tregs. It pointed out. Researchers may find that there is no difference in the number of Tregs in skin tumors between mice with liver cancer and mice without liver cancer, because these cells also alter the function of a group of other immune system cells. No, but I find the quality is different. An important difference. Because liver tumors can promote Tregs and block the T cell response that resists tumors, the researchers tested whether these two drugs can cover the effects of Tregs. First, the first drug can block the T cell checkpoint inhibitor CTLA-4, and these cells can be released to attack cancer. In the 1990s, researchers conducted pioneering studies on CTLA-4 to help lay the foundation for its application in cancer immunotherapy. The second drug is another drug. Anti-CTLA-4 compounds that can directly target Tregs cells and eliminate their number can restore the effect of anti-PD-1 therapy, but anti-CTLA-4 drugs that eliminate Treg are more effective.

　　In the future, researchers hope to apply this combination therapy to past patients who have a weak response to treatment. Finally, Researcher Li said that no immunotherapy is so precise. By using Tregs scavengers as a supplement to cancer cell metastasis immunotherapy from the beginning, it may be possible to treat cancer patients with liver metastases more effectively.