In the progressing field of immunotherapy, surprisingly little is known about immunity to metastatic tumors in locations such as lymph nodes, a frequent place where cancers first spread. Not only do lymph nodes act as a gateway for cancer cells to travel throughout the body, but they are also home to infection-fighting white blood cells called T cells. In some cases, T cells in lymph nodes activate to kill invading cancer cells. In other cases, that process clearly fails.<\/p>\n
To address the need to understand why, researchers in the laboratory of Mary Jo Turk, PhD, Co-Director of the Immunology and Cancer Immunotherapy Research Program at Dartmouth\u2019s and Dartmouth-Hitchcock\u2019s Norris Cotton Cancer Center (NCCC) have spent the past year studying immunity to metastatic cancer within lymph nodes.<\/p>\n
While T cells can freely travel from lymph nodes into the bloodstream and back to the lymph nodes, researchers in Turk\u2019s lab have discovered a novel population of tumor-fighting T cells that do not circulate, but rather stay in lymph nodes where they provide protection against melanoma. \u201cThese T cells, for whatever reason, have changed their program and stay in the lymph nodes where they persist and kill tumor cells for many months while never entering circulation,\u201d says Turk.<\/p>\n
These long-lived T cells, called \u201clymph node resident memory T\u00a0<\/sub>cells,\u201d were shown to counteract melanoma spreading in mice. Turk\u2019s team found that when melanoma cells were put back into mice that had been cured of cancer with immunotherapy a month earlier, the lymph nodes were still resistant to the cancer\u2014the melanoma would not grow.<\/p>\n \u201cWe also identified T cells with similar characteristics in melanoma-invaded patient lymph nodes, showing that similar populations exist in humans,\u201d reveals Turk.<\/p>\n Computational analysis of melanoma specimen data from The Cancer Genome Atlas revealed that the presence of T cells with this gene signature predicted better outcomes and improved survival for human melanoma patients with lymph node metastases. \u201cThese studies reveal a new population of T cells that is vital for counteracting the earliest stages of cancer metastasis,\u201d says Turk.<\/p>\n Although the concept of T cells taking up residence in lymph nodes is not entirely new, it has never been shown in cancer. The team\u2019s findings, \u201cResident memory T cells in regional lymph nodes mediate immunity to metastatic melanoma,\u201d are newly published in Immunity<\/i><\/em>.<\/p>\n The team, including clinicians at Dartmouth-Hitchcock Medical Center, as well as researchers at Baylor College of Medicine led by computational biologist, Chao Cheng, PhD, employed innovative sequencing techniques to identify the unique transcriptional profile that makes these resident T cells specific to lymph nodes and to cancer. \u201cWe found that these cells have a unique gene expression profile that differentiates them from cells in circulation, and from memory T cells that reside in and protect other tissues such as the skin,\u201d says Cheng.<\/p>\n Other collaborators on this work include the University of Michigan and University of Texas, San Antonio.<\/p>\n In the coming year, the Turk research team hopes to better understand how these memory T cells are most effectively generated and activated within lymph nodes. The ultimate goal is to understand how memory T cells can be positioned throughout tissues to efficiently block cancer from spreading.<\/p>\n Mary Jo Turk, PhD,<\/b><\/strong> is the O. Ross McIntyre, MD, Endowed Professor and Professor of Microbiology and Immunology at the Geisel School of Medicine at Dartmouth, and the Co-Director of the Immunology and Cancer Immunotherapy Research Program at Dartmouth\u2019s and Dartmouth-Hitchcock\u2019s Norris-Cotton Cancer Center. Her laboratory's research focuses on generating memory T cell responses for long-lived immunity to cancer.<\/p>\n Chao Cheng, PhD,<\/b><\/strong> is an associate professor of the Dan L. Duncan Comprehensive Cancer Center, the Institute for Clinical and Translational Research, and Department of Medicine at Baylor College of Medicine. His laboratory focuses on computational method development and application to cancer systems biology and cancer immunology.<\/p>\n About Norris Cotton Cancer Center<\/b><\/strong><\/p>\n Norris Cotton Cancer Center<\/a>, located on the campus of Dartmouth-Hitchcock Medical Center<\/a> (DHMC) in Lebanon, NH, combines advanced cancer research at Dartmouth College\u2019s Geisel School of Medicine in Hanover, NH with the highest level of high-quality, innovative, personalized, and compassionate patient-centered cancer care at DHMC, as well as at regional, multi-disciplinary locations and partner hospitals throughout NH and VT. NCCC is one of only 51 centers nationwide to earn the National Cancer Institute\u2019s prestigious \u201cComprehensive Cancer Center\u201d designation, the result of an outstanding collaboration between DHMC, New Hampshire\u2019s only academic medical center, and Dartmouth College. Now entering its fifth decade, NCCC remains committed to excellence, outreach and education, and strives to prevent and cure cancer, enhance survivorship and to promote cancer health equity through its pioneering interdisciplinary research. Each year the NCCC schedules 61,000 appointments seeing nearly 4,000 newly diagnosed patients, and currently offers its patients more than 100 active clinical trials.<\/p>\n About the Geisel School of Medicine<\/b><\/strong><\/p>\n Founded in 1797, the\u00a0Geisel School of Medicine at Dartmouth strives to improve the lives of the communities it serves through excellence in learning, discovery, and healing. The Geisel School of Medicine is renowned for its leadership in medical education, healthcare policy and delivery science, biomedical research, global health, and in creating innovations that improve lives worldwide. As one of America\u2019s leading medical schools, Dartmouth\u2019s Geisel School of Medicine is committed to training new generations of diverse leaders who will help solve our most vexing challenges in healthcare.<\/p>\n About Dartmouth-Hitchcock Health<\/b><\/strong><\/p>\n Dartmouth-Hitchcock<\/a>\u00a0Health (D-HH), New Hampshire\u2019s only academic health system and the state\u2019s largest private employer, serves a population of 1.9 million across northern New England. D-H provides access to more than 2,000 providers in almost every area of medicine, delivering care at its flagship hospital, Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, NH. DHMC was named again in 2020 as the #1 hospital in New Hampshire by\u00a0U.S. News & World Report<\/em><\/a>, and recognized for high performance in 9 clinical specialties and procedures. Dartmouth-Hitchcock also includes the\u00a0Norris Cotton Cancer Center<\/a>, one of only 51 NCI-designated Comprehensive Cancer Centers in the nation; the\u00a0Children's Hospital at Dartmouth-Hitchcock<\/a>, the state\u2019s only children\u2019s hospital; affiliated member hospitals in Lebanon, Keene, and New London, NH, and Windsor, VT, and Visiting Nurse and Hospice for Vermont and New Hampshire; and 24 Dartmouth-Hitchcock clinics that provide ambulatory services across New Hampshire and Vermont. The D-H system trains nearly 400 residents and fellows annually, and performs world-class research, in partnership with the\u00a0Geisel School of Medicine\u00a0at Dartmouth<\/a>\u00a0and the\u00a0White River Junction VA Medical Center<\/a>\u00a0in White River Junction, VT.<\/p>\n","protected":false},"excerpt":{"rendered":" Researchers in the laboratory of Mary Jo Turk, PhD, Co-Director of the Immunology and Cancer Immunotherapy Research Program at Dartmouth\u2019s and Dartmouth-Hitchcock\u2019s Norris Cotton Cancer Center have spent the past year studying immunity to metastatic cancer within lymph nodes.<\/p>\n","protected":false},"author":143,"featured_media":14625,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1,182,8],"tags":[176],"class_list":["post-15315","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","category-press-release-news","category-research","tag-nccc","author-143"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-content\/uploads\/sites\/2\/2021\/03\/MaryJoTurk.jpg","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p4r3h1-3Z1","_links":{"self":[{"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/posts\/15315","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/users\/143"}],"replies":[{"embeddable":true,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/comments?post=15315"}],"version-history":[{"count":1,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/posts\/15315\/revisions"}],"predecessor-version":[{"id":15316,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/posts\/15315\/revisions\/15316"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/media\/14625"}],"wp:attachment":[{"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/media?parent=15315"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/categories?post=15315"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/tags?post=15315"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}