Source: Bio Valley Original 2023-09-30 19:51
Scientists from the Salk Institute and other institutions have discovered a link between T cell exhaustion and the body’s sympathetic stress response (“fight or flight”) by studying multiple cancer types in mouse and human tissue samples.
Even killer T cells (specializedimmunitycells) work around the clock to seek out and destroy cancer cells, which can also cause them to become exhausted. If scientists can understand why killer T cells become exhausted, they may be able to create more resilient cancer-fighting cells. .Recently, an article was published in an international magazineNatureIn the previous research report titled “Beta-1 Adrenergic Receptor links sympathetic nerves to T cell exhaustion”, scientists from the Salk Institute and other institutions studied multiple cancer types in mouse and human tissue samples and discovered that T link between cell exhaustion and the body’s sympathetic stress response (“fight or flight”). In addition, they found that the interaction between killer T cells and sympathetic stress response hormones may be blocked by beta-blockers, a class of Drugs used in humans to control blood pressure and heart rate) are inhibited, thereby producing killer T cells that can more effectively fight tumors.
In the article, the researchers establish a novel link between the sympathetic stress response and how the immune system responds to cancer. In addition, they demonstrate that combining beta blockers with current immunotherapies may improve the immune system by enhancing killer T cells. Cell function to improve cancer treatment. Researcher Professor Susan Kaech said that there is no doubt that immunotherapy has revolutionized the treatment of cancer patients, but there are still many patients who do not respond well to treatment. Finding that our nervous system can inhibit the function of immune cells that destroy cancer may provide Thinking about how to restore T cell function in tumors has opened up new avenues. The sympathetic nervous system is primarily responsible for mediating the body’s stress response, known as the “fight or flight response.” However, researchers don’t know how the body’s nerves regulate the immune response to fight infection or cancer.
In this study, the researchers focused on the sympathetic nerves that innervate the body’s organs and produce the messenger hormone norepinephrine, a stress hormone. They then used various cancers in tissue samples from mice and humans. and chronic disease models to analyze when and how killer T cells are affected by sympathetic nerves. It was found that sympathetic nerves produce norepinephrine, which binds to killer T cells through the use of a receptor called ADRB1. Depleted killer T cells express more ADRB1 receptors than their functional counterparts. body, allowing T cells to listen for norepinephrine being released by the nerves.
Reducing stress on T cells may lead to better treatments for cancer patients.
Image Source:Nature (2023). DOI:10.1038/s41586-023-06568-6
To test whether the exhaustion of killer T cells could be prevented, the researchers tested two methods of blocking norepinephrine’s interaction with ADRB1, either by removing ADRB1 completely or using beta-blockers to impair ADRB1 function. This will produce more functional killer T cells to better destroy cancer cells. The researchers found that exhausted T cells were not able to “listen” to nerves from a distance, but were able to swarm around them in tissues. Surprisingly, the ADRB1 receptor provided key instructions for T cells to migrate near nerves. , which in turn inhibits its function and makes it worse at fighting cancer.Researchers believe that the innervation of tumors istumor immunityAn understudied area of science, current research has found that nerves promote the process of T cell exhaustion in tumors, and that over time, T cells also become exhausted and become less effective in the fight against tumors. Powerful; if researchers can unravel the details behind neural suppression of the body’s immune response to cancer and how exhausted T cells move toward neural tissue, perhaps they can begin to target this process therapeutically.
Researchers hope to expand their understanding of the environment of exhausted T cells to better understand why stress makes us heavier; “We may be able to find a new pathway that harnesses beta-blockade,” says Globig. blockers to create more resilient killer T cells that resist exhaustion and better help fight cancer.Since beta-blockers are now widely used clinically, researchers also hope tolung cancerImplement new anti-cancer strategies in patients as soon as possible and propose new anti-cancer strategies as soon as possible. By collaborating with clinicians, researchers hope to study more tissue samples from human cancer patients, thereby enriching research findings and providing beta-blockers with new ways to treat cancer. Further evidence of effectiveness in therapy.
In summary, in this study, researchers uncovered a new mechanism by which the body’s anti-tumor ability can be restored by blocking CD8+ T cells. (Bio ValleyBioon.com）
Original source:
Globig, AM., Zhao, S., Roginsky, J. et al. The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion. Nature (2023). doi：10.1038/s41586-023-06568-6
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2023-09-30 11:51:00
