{"id":95958,"date":"2021-07-19T18:07:44","date_gmt":"2021-07-19T22:07:44","guid":{"rendered":"http:\/\/www.bumc.bu.edu\/busm\/?p=95958"},"modified":"2021-08-24T12:22:31","modified_gmt":"2021-08-24T16:22:31","slug":"researchers-discover-how-cancer-cells-that-spread-to-lymph-nodes-avoid-immune-destruction","status":"publish","type":"post","link":"https:\/\/www.bumc.bu.edu\/camed\/2021\/07\/19\/researchers-discover-how-cancer-cells-that-spread-to-lymph-nodes-avoid-immune-destruction\/","title":{"rendered":"Researchers Discover How Cancer Cells that Spread to Lymph Nodes Avoid Immune Destruction"},"content":{"rendered":"

<\/em>Lymph nodes are critical to the body\u2019s immune response against tumors but paradoxically, cancer cells that spread, or metastasize, to lymph nodes can often avoid being eliminated by immune cells. Recent experiments by investigators at Massachusetts General Hospital (MGH) and Boston University School of Medicine (BUSM) provide insights on the details behind this immune evasion, which could help scientists develop strategies to overcome it. The findings<\/a> are published in Nature Biomedical Engineering<\/em>.<\/p>\n

\u201cWe know that lymph nodes are often the first place cancer spreads as it progresses. We also know that our immune system can attack and kill cancer cells,\u201d explains senior and co\u2013corresponding author Timothy P. Padera, PhD, an investigator in Radiation Oncology at MGH and a 2021-2026 MGH Research Scholar. \u201cOne of the perplexing questions that has been at the core of the recent work in my lab is how can organs that generate our immune responses\u2014lymph nodes\u2014permit cancer cells to survive and take them over instead of attacking them? This was the driving motivation behind this study.\u201d<\/p>\n

By analyzing patient tissue from breast, colon, and head and neck cancers, combined with animal models of breast cancer lymph node\u00a0metastases, Padera and his colleagues showed that immune cells called T cells are abundant in metastatic lymph nodes but fail to penetrate\u00a0tumors that have spread to such nodes. The team measured increased physical forces, known as solid stress, in lymph nodes with metastatic cancer. \u201cWe hypothesized that solid stress in lymph node tumors can impair both blood flow and the T cell trafficking capacity of blood vessels in lymph nodes,\u201d says lead and co\u2013corresponding author Dennis Jones, PhD, an assistant professor of Pathology & Laboratory Medicine at BUSM.<\/p>\n

The scientists then developed a device to compress lymph nodes in order to simulate the gradual growth of lymph node metastases. When they applied compressive force to lymph nodes, there was a clear link between physical force and disruption of T cell entry into lymph nodes. \u201cOur findings indicate that as cancer cells grow in the lymph node, they reorganize and alter the lymph node, disabling critical functional responses of the immune system,\u201d says Padera. \u201cBy understanding how cancer cells are disabling lymph node function, we hope to fight back to help the lymph nodes generate anti-cancer immune responses, which will help fight cancer cells everywhere in the body.\u201d<\/p>\n

Alleviating solid stress with the blood pressure drug losartan boosted the numbers of blood vessels and T cells in lymph node metastases, suggesting that alleviating solid stress is a potential strategy to improve T cell entry into tumors.<\/p>\n

\u201cOur work now leads to many important additional questions,\u201d says Jones. \u201cDoes losartan treatment combined with immunotherapy cause the eradication of metastatic cancer cells in lymph nodes by T cell killing? And further, does this lead to a strong systemic anti-cancer immune response that helps clear the cancer from the entire body?\u201d Jones notes that finding the answers to these questions could lead to new treatment strategies for patients with metastatic cancer.<\/p>\n

Padera is an associate professor of Radiation Oncology at Harvard Medical School. In addition to Jones and Padera, co-authors include Zixiong Wang, Ivy X. Chen, Sue Zhang, Rohin Banerji,\u00a0Pin-Ji Lei, Hengbo Zhou, Victoria Xiao, Cecilia Kwong, Jan Willem M. van Wijnbergen, Ethel R. Pereira, Benjamin J. Vakoc, Peigen Huang, and Hadi T.\u00a0Nia.<\/p>\n

\n

This study was supported by the National Institutes of Health, the Massachusetts General Hospital Executive Committee on Research, the Mass General Research Institute Research Scholars Program, and the METAvivor organization.<\/p>\n","protected":false},"excerpt":{"rendered":"

Blood pressure drug losartan may help thwart this evasion tactic.<\/p>\n","protected":false},"author":903,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[91,90],"tags":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/95958"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/users\/903"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/comments?post=95958"}],"version-history":[{"count":4,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/95958\/revisions"}],"predecessor-version":[{"id":96759,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/95958\/revisions\/96759"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/media?parent=95958"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/categories?post=95958"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/tags?post=95958"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}