Scientists from the University of Pittsburgh and other institutions said in the latest research report published in the International Journal of Natural Immunity that blocking "immune memory checkpoints" identified in immune cells may improve immunotherapy. And it helps effectively prevent the recurrence of cancer. Immunotherapy drugs that can regulate the human immune system against cancer have completely changed the treatment of many cancers. It works by blocking checkpoint inhibitory proteins (such as PD1) and eliminates its impact on the immune system. For cancer killer T cells, only about one-third of patients respond to these drugs.
Dario (Dario A.A.) researcher Wignali said that we still need to do a lot of work to improve the effectiveness of cancer immunotherapy. In this study, the researchers revealed a new and important biological anti-tumor mechanism that can be used to provide long-term and long-term immune responses to tumors. Researchers found that a protein called NRP1 (neuropyrin-1) plays an important role in suppressing the body's immune response to cancer. Everyone knows that NRP1 exists on the surface of other T cells, but researchers want to know whether NRP1 can change the function of killer T cells. This may be similar to other immune checkpoint molecules, which can inhibit tumor growth by preventing the expression of NRP1. In this article, the researchers developed a genetically modified mouse that can only eliminate NRP on the surface of killer T cells. When tumor cells are transplanted into a mouse model, the researchers compared normal animals. Tumors in these mice grew as observed by blocking other checkpoint proteins. Its growth is not very slow, but the result is just the opposite. The researchers did not observe any changes.
Researcher Liu said that removing NRP1 does not seem to affect the body's anti-tumor immunity, so does NRP1 change the tumor memory ability of the human immune system? After that, the tumor was excised and the cancer cells were transplanted to another part of the mouse body to simulate the recurrence of cancer after the tumor patient, and a huge effect was observed compared with normal mice. Yes, mice with gene deletion of NRP1 in killer T cells may have better protection against the development of secondary tumors and respond more positively to anti-PD1 immunotherapy. Also a possibility. Later, the researchers further studied and found that neural pyrin can regulate the fate of T cell development and establish immune memory in the body. The use of RP1 promotes the depletion of killer T cells and is not particularly effective against cancer cells. In order to obtain long-term protection, the removal of NRP1 will increase the immune memory of T cells, so that the body will produce a stronger immune response when it encounters a tumor again. These studies in mice may be related to the study of T cells isolated from the blood of patients with skin cancer or head and neck cancer. Compared with patients with early head and neck cancer, patients with advanced head and neck cancer have memory in the body. Killer T cell subsets usually express high levels of NRP1. In advanced skin cancer patients receiving multiple immunotherapies, high levels of killer T cell NRP1 are usually associated with decreased response to treatment and decreased levels of memory T cells. Low is directly related. Researcher Vignari has a new understanding of how to control anti-tumor immunity in this study, which may provide new treatment opportunities and ideas for promoting and enhancing the long-term anti-tumor response of cancer patients in the future.
Finally, the researchers said that drugs targeting NRP1 are currently being used clinically in combination with anti-PD1 immunotherapy. These clinical trials revealed the important role of immune memory in fighting cancer. Subsequent researchers will continue their research to find new ways to reduce the rate of cancer recurrence by enhancing the host's immune memory.