Researchers find immune cells that guard frequent site of cancer spread

LEBANON, NH – 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.

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’s and Dartmouth-Hitchcock’s Norris Cotton Cancer Center (NCCC) have spent the past year studying immunity to metastatic cancer within lymph nodes.

While T cells can freely travel from lymph nodes into the bloodstream and back to the lymph nodes, researchers in Turk’s 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. “These 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,” says Turk.

These long-lived T cells, called “lymph node resident memory T cells,” were shown to counteract melanoma spreading in mice. Turk’s 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—the melanoma would not grow.

“We also identified T cells with similar characteristics in melanoma-invaded patient lymph nodes, showing that similar populations exist in humans,” reveals Turk.

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. “These studies reveal a new population of T cells that is vital for counteracting the earliest stages of cancer metastasis,” says Turk.

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’s findings, “Resident memory T cells in regional lymph nodes mediate immunity to metastatic melanoma,” are newly published in Immunity.

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. “We 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,” says Cheng.

Other collaborators on this work include the University of Michigan and University of Texas, San Antonio.

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.

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Mary Jo Turk, PhD, 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’s and Dartmouth-Hitchcock’s Norris-Cotton Cancer Center. Her laboratory's research focuses on generating memory T cell responses for long-lived immunity to cancer.

Chao Cheng, PhD, 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.

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About Norris Cotton Cancer Center

Norris Cotton Cancer Center, located on the campus of Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, NH, combines advanced cancer research at Dartmouth College’s 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’s prestigious “Comprehensive Cancer Center” designation, the result of an outstanding collaboration between DHMC, New Hampshire’s 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.

About the Geisel School of Medicine

Founded in 1797, the Geisel 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’s leading medical schools, Dartmouth’s Geisel School of Medicine is committed to training new generations of diverse leaders who will help solve our most vexing challenges in healthcare.

About Dartmouth-Hitchcock Health

Dartmouth-Hitchcock Health (D-HH), New Hampshire’s only academic health system and the state’s 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 U.S. News & World Report, and recognized for high performance in 9 clinical specialties and procedures. Dartmouth-Hitchcock also includes the Norris Cotton Cancer Center, one of only 51 NCI-designated Comprehensive Cancer Centers in the nation; the Children's Hospital at Dartmouth-Hitchcock, the state’s only children’s 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 Geisel School of Medicine at Dartmouth and the White River Junction VA Medical Center in White River Junction, VT.