癌细胞,免疫系统 z-bo 2020-10-30 361

　　In a new study, researchers from the University of California, Los Angeles found that a drug that activates the body’s natural defense system like a virus may also make certain invisible melanomas visible to the immune system, making immunotherapy better Target them. These findings provide the possibility to use virus-simulating drugs to overcome the immunotherapy resistance of tumors with interferon signaling defects, and help develop more personalized treatments for cancer patients that are difficult to treat.

　　Corresponding author of the paper, Dr. Anusha Kalbasi, assistant professor of radiation oncology at the University of California, Los Angeles School of Medicine, said, “Most immunotherapy methods rely on the ability of T cells to recognize and kill tumor cells. However, in some patients, tumors can participate in Genes in the interferon signaling pathway are mutated to evade the immune system. This is a key pathway because it usually allows tumors to increase their antigen presentation. This is an intricate mechanism that makes tumors visible to T cells."

　　Interferon is a protein in the cell that prevents the virus from replicating and reminds the immune system to mobilize power to deal with viral infections. Activating the interferon signal in the tumor helps slow tumor division and can lead to the release of molecules that recruit more immune cells into the tumor. Kalbasi said, "This coordinated effort due to interferon signal transduction can help the immune system better recognize and kill tumor cells."

　　These researchers tried for the first time to overcome interferon signaling defects by adopting adoptive T cell therapy. Adoptive T cell therapy is an immunotherapy that involves extracting T cells from patients and genetically modifying them in the laboratory to identify And kill cancer cells. They found that these T cells are still ineffective against tumors that are defective in interferon signaling.

　　These researchers then genetically modified mouse melanoma cells with a gene called NLRC5. NLRC5 can increase antigen presentation and restore the effectiveness of T cells even in the absence of interferon signal transduction. Although this method is effective in mice, genetic modification of tumor cells in humans is not that simple.

　　Kalbasi and his colleagues turned to a virus-simulating drug called BO-112, which can activate the virus-sensing pathway in tumors. When the drug was injected directly into the tumor in the laboratory, they found that activation of the virus-sensing pathway would increase antigen presentation even in the presence of a defect in the interferon signal. Therefore, these tumors can be recognized and killed by T cells.

　　The first author of the paper, Dr. Antoni Ribas, professor of medicine at the University of California, Los Angeles School of Medicine, said, “This research helps us understand the interdependence between interferon signaling and antigen presentation, which allows us to understand how tumor cells are affected by the immune system. Recognition has important insights. New strategies to promote antigen presentation make tumors more visible to the immune system, which will make immunotherapy effective for more tumor types."

　　These findings also highlight the potential of other promising clinical methods (such as CAR-T cell therapy) that can bypass tumor interferon signaling and antigen presentation. Even in the absence of antigen presentation, CAR-T cells can recognize and kill tumor cells.

　　Kalbasi is currently leading a human clinical trial of a combination of the immune checkpoint blocking drug nivolumab and BO-112 in patients with certain types of sarcoma who undergo radiotherapy after surgery. The idea is to activate the immune system to fight the tumor in the patient while the tumor is still in the body.