{"id":42379,"date":"2023-09-20T07:52:13","date_gmt":"2023-09-20T14:52:13","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=42379"},"modified":"2024-01-30T14:10:50","modified_gmt":"2024-01-30T22:10:50","slug":"reducing-stress-on-t-cells-makes-them-better-cancer-fighters","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/reducing-stress-on-t-cells-makes-them-better-cancer-fighters\/","title":{"rendered":"Reducing stress on T cells makes them better cancer fighters"},"content":{"rendered":"

LA JOLLA\u2014Even for killer T cells\u2014specialized immune cells\u2014seeking and destroying cancer cells around the clock can be exhausting. If scientists can understand why killer T cells become exhausted, then they can create more resilient cancer-killing cells. \r\n<\/p>

\r\nIn a new study, Salk Institute scientists discovered a relationship between killer T cell exhaustion and the body\u2019s sympathetic stress response (\u201cfight-or-flight\u201d) in varying cancer types in mouse and human tissue samples. What\u2019s more, the team found that the interaction between killer T cells and sympathetic stress response hormones can be inhibited with beta-blockers\u2014a class of drugs already used in humans for controlling blood pressure and heart rate\u2014to create killer T cells that fight the tumor more efficiently.\r\n<\/p>\r\n

\"From
From left: Susan Kaech and Anna-Maria Globig.
Click here<\/a> for a high-resolution image.
Credit: Salk Institute<\/figcaption><\/figure>\r\n\r\n

\r\nThe findings, published in Nature<\/a><\/em> on September 20, 2023, establish a new link between the sympathetic stress response and how the immune system responds to cancer. Additionally, they demonstrate the benefit of pairing beta-blockers with existing immunotherapies to improve cancer treatment by bolstering killer T cell function. \r\n<\/p>

\r\n\u201cThere is no question immunotherapy has revolutionized cancer patient treatment\u2014but there are many patients for whom it\u2019s ineffective,\u201d says Professor Susan Kaech<\/a>, senior author and director of Salk\u2019s NOMIS Center for Immunobiology and Microbial Pathogenesis. \u201cFinding that our nervous system can suppress the function of cancer-destroying immune cells opens up entirely new ways to think about how to rejuvenate T cells in tumors.\u201d\r\n<\/p>

\r\nThe sympathetic nervous system is responsible for mediating the body\u2019s stress response, also known as the fight-or-flight response. However, little was known about how the nerves regulate the immune response to infections or cancer. \r\n<\/p>

\r\nThe researchers focused on sympathetic nerves that innervate our organs and produce the messenger hormone noradrenaline, which is also a stress hormone. The scientists used a variety of cancer and chronic illness models in mice and human tissue samples to study when and how killer T cells are influenced by the sympathetic nerves. \r\n<\/p>\r\n\r\n

\"Exhausted
Exhausted killer T cells with higher expression of the noradrenaline receptor ADRB1 (cyan) surround sympathetic nerves (yellow) in a virally infected spleen. Killer T cells without ADRB1 (red) do not surround the sympathetic nerves (yellow).
Click here<\/a> for a high-resolution image.
Credit: Salk Institute<\/figcaption><\/figure>\r\n\r\n

\r\nThey found that the sympathetic nerves were producing noradrenaline, which was binding to killer T cells using a receptor called ADRB1. Exhausted killer T cells expressed more ADRB1 receptors than their functional counterparts, allowing the T cells to \u201clisten\u201d to the noradrenaline released by the nerves.\r\n<\/p>

\r\nTo test whether killer T cell exhaustion could be prevented, the researchers tested two approaches to intercepting noradrenaline and ADRB1 interaction: either removing ADRB1 altogether or impairing ADRB1 function with beta-blockers, which resulted in more-functional killer T cells that were better at destroying cancer cells. \r\n<\/p>

\r\nThe authors also found that the exhausted T cells do not just listen to nerves from afar, but cluster right around them in tissues. Surprisingly, the ADRB1 receptor provided the T cells with critical instructions to migrate near the nerves, which in turn suppressed their functions\u2014making them worse at fighting cancer. \r\n<\/p>

\r\n\u201cThe innervation of tumors is an understudied area of tumor immunology. Our study has now uncovered that nerves contribute to the process of T cell exhaustion in tumors, where T cells become worn out and less powerful in their fight against the tumor over time,\u201d says first author Anna-Maria Globig, a postdoctoral researcher in Kaech\u2019s lab. \u201cIf we can unravel the details of how nerves suppress the body\u2019s immune response to cancer and why the exhausted T cells move towards the nerves, we can begin to target this process therapeutically.\u201d\r\n<\/p>

\r\nAccording to Kaech, the researchers hope to expand their understanding of the exhausted killer T cell environment to learn more about why stress makes us sicker.\r\n<\/p>

\r\n\u201cWe were able to find a new pathway that we can target with beta-blockers to create more resilient killer T cells that resist exhaustion and fight cancer better,\u201d says Globig.\r\n<\/p>

\r\nSince beta-blockers are already clinically used, the team also hopes to implement their proposed cancer-fighting regimen soon in patients with lung cancer. By partnering with clinicians, they hope to study more human cancer tissue samples to enrich their findings and provide further evidence of the efficacy of beta-blockers in cancer treatment.\r\n<\/p>

\r\nOther authors include Steven Zhao, Jessica Roginsky, Natalia Avina-Ochoa, Filipe Hoffmann, Gokhan Senturk, Dan Chen, Carolyn O\u2019Connor, and Samuel Pfaff of Salk; Vivien Maltez and Ronald Germain of the National Institutes of Health; Juan Guiza, Omkar Chaudhary, Jiawei Wang, Kurt Schalper, and Brinda Emu of the Yale School of Medicine; and Maximilian Heeg of UC San Diego.\r\n<\/p>

\r\nThe work was supported by the German Research Foundation (GL 991\/1-1), the NOMIS Foundation, and the National Institutes of Health (grants K00CA222741, 5R01 CA240909, 5R01 CA216101, R37CA245154, R01CA262377, P50CA196530).\r\n<\/p>","protected":false},"featured_media":42675,"template":"","faculty":[311],"disease-research":[46,122,331],"class_list":["post-42379","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-susan-kaech","disease-research-cancer-biology","disease-research-immune-system-biology","disease-research-protein-interactions"],"acf":[],"yoast_head":"\nReducing stress on T cells makes them better cancer fighters - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/reducing-stress-on-t-cells-makes-them-better-cancer-fighters\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Reducing stress on T cells makes them better cancer fighters - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Even for killer T cells\u2014specialized immune cells\u2014seeking and destroying cancer cells around the clock can be exhausting. 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