Nat Commun: how cancer and the immune system compete in arms! In depth interpretation!

February 18, 2020 / BIOON / -- recently, an international journal Nature Communications In the previous research report, scientists from London Cancer Research Institute and other institutions found that in the "evolutionary arms race" between cancer and the immune system, invasive and highly mutated cancer may evolve a certain escape mechanism under the immune attack of the host organism Photo source: Katharina von loga, Biomedical Research Centre There are a lot of defects in the DNA error repair system of esophageal cancer and gastric cancer, which often lead to a large number of mutations, so as to have a certain tolerance to chemotherapy and other treatment methods; however, a large number of mutations mean that it is "foreign" to the immune system, so that it is more vulnerable to attack, but also more vulnerable to the impact of new immunotherapy; researchers found that, high Mutated tumors often can quickly evolve special strategies to effectively distinguish the host immune system and outsiders, so as to avoid attack The findings also highlight the important role of Darwinian evolution in cancer and cancer How to react to the immune system may help researchers optimize immunotherapy and new drugs, such as chemotherapy, in the future; in this study, researchers want to understand how cancer adapts and adapts to changes in the environment, such as avoiding the host immune system or developing a certain tolerance to the treatment The researchers want to design a drug discovery program to meet the challenge of cancer evolution and drug tolerance to cancer treatment In this paper, the researchers analyzed the genetic structure of four kinds of tumors from the stomach and esophagus, which have one or more important DNA repair gene defects, which will make them highly mutated At the same time, the researchers also analyzed the genetic composition of 7 different regions and cancer spreading regions in each patient's body tumor The results showed that the highly mutated gastric tumor had a high level of genetic variation, reaching an average of nearly 2000 different genetic errors, which was far higher than 436 genetic errors in skin cancer Different regions of the same tumor can also show extreme differences in mutations, compared to other tumors analyzed in the study There are many types, which support Darwin's theory of rapid evolution Importantly, gastric cancer and esophageal cancer with the highest immune cell infiltration have multiple mutations, which make it difficult to avoid the host's immune attack These mutations include B2M, The mutations of HLA and Jak1 / 2 genes normally help immune cells recognize and attack cancer cells When the gene loses normal function, the immune system can not defeat cancer cells at a fixed point, even if there are a large number of mutations The researchers believe that highly mutated cancers will be subject to particularly strong selective pressure from the immune system, which will make them use of huge genetic variation to evolve faster than other types of cancer, making it difficult to treat; however, highly mutated gastric cancer and esophageal cancer are particularly sensitive to the new immunotherapy, so the immune system can effectively resist the rapidly evolving Tumor The findings further prove that high mutation rates have evolutionary consequences in triggering the arms race between the immune system and cancer, which may help to understand why these cancers are often sensitive to immunotherapy The results of this study may help researchers further elucidate the impact of cancer evolution on host immune response and the potential benefits of immunotherapy in the treatment of similar highly mutated intestinal tumors They hope to use similar immune system strategies to help resist cancer tolerance to chemotherapy Marco According to Dr gerlinger, the latest research shows that in highly mutated tumors, cancer and the immune system may be involved in the arms race to explain highly mutated tumors in detail The coevolution mechanism with immune cells may help host immune system to monitor cancer changes in real time, so as to use immunotherapy to change the balance between them, so as to prolong the life of patients In the next step, researchers will clarify the evolutionary connection between highly mutated tumors and the immune system, so as to help observe the potential benefits of immunotherapy in the treatment of colorectal cancer as part of new clinical trials; cancer evolution is a huge challenge faced by researchers in the process of cancer research and treatment development, which depends on the deep understanding of tumor by researchers How to react to therapy to overcome the effect of drugs At present, researchers are very interested in studying how cancer evolves with the host immune system and how they respond to changes If there is no treatment, cancer may win the arms race, but researchers can change this balance through well-designed immunotherapy, so that it is beneficial to the host immune system Now we are eager to see researchers use their new insights on cancer evolution to predict cancer's response to immunotherapy, and ultimately enhance the way we use immunotherapy to maximize its effectiveness This study emphasizes the importance of understanding the evolution of cancer and the selective pressure that may be exerted by the immune system and tumor development of patients The challenge to improve the prognosis of cancer patients is to fully understand the evolution of cancer, which may mean that scientists should study samples from different cancer patients Up to now, researchers have Tumor samples from four relatively rare cancer patients were analyzed There is still a long way to go in the future, but researchers hope that with the discovery of cancer evolution, they will be able to find more ways to treat cancer patients in the future Reference materials: [1] cancers engaged in evolutionary arms race with immune system by Institute of cancer research [2] von logo, K., woolston, A., Punta, M et al Extreme intratumour ergonomicity and driver evolution in mismatch repair deficient Gastro oesophageal cancer NAT Commission 11, 139 (2020) Doi: 10.1038/s41467-019-13915-7