Researchers at Dartmouth’s and Dartmouth-Hitchcock’s Norris Cotton Cancer Center (NCCC), New Hampshire’s only NCI-designated Comprehensive Cancer Center, have found that a certain subpopulation of cells that enters a patient’s skin and blood during immunotherapy is behind the excellent and long-lasting immune responses to cancer that some survivors develop. No prior study has demonstrated cellular evidence of such long-lived immunity to cancer.
Some melanoma patients respond very well to immunotherapy, experiencing profound and durable tumor regression. A fraction of these patients will also develop autoimmunity against their normal melanocytes—the cells that give rise to melanoma—a phenomenon called vitiligo. Melanoma survivors with vitiligo have long been recognized as a special group with an outstanding prognosis, and a strong response of immune system cells called T cells.
Immunotherapy researchers at NCCC, led by Mary Jo Turk, PhD, the O. Ross McIntyre, MD, Professor at the Geisel School of Medicine, and surgical oncologist Christina Angeles, MD (now of University of Michigan), have discovered how a subset of T cells known as memory T cells are generated in melanoma survivors with vitiligo and able to function for years after a tumor is gone.
“We are trying to understand how immune responses against cancer can persist over long periods of time in patients who have excellent responses to immunotherapy,” says Turk. “Our study was aimed at discovering where T cells go, what they do and how long they last in these patients. Some T cells last a short time, but others, known as memory T cells, can last for years. The goal of this work was to understand how memory T cells are generated in these patients.”
The team’s findings, entitled “Resident and circulating memory T cells persist for years in melanoma patients with durable responses to immunotherapy,” are newly published in Nature Cancer. The extensive collaboration between scientists, surgeons, and oncologists required harvesting tumors, blood, and skin from melanoma patients over a period of several years. Patient specimens were analyzed using state-of-the-art technologies called single cell RNA sequencing and T cell receptor sequencing.
"Finding that T cells can persist for years throughout skin and blood and understanding what defines such durable immune responses in melanoma patients will lead to better design of therapies to achieve such responses," says Turk.
Co-leading this work was Christina Angeles, MD, FACS, who designed and led clinical aspects of the study while at NCCC and serves as co-corresponding author on the paper. Angeles is now a surgical oncologist at Rogel Cancer Center, University of Michigan.
This work was funded by the National Institutes of Health, the American Cancer Society, the Dartmouth CTSA, Dow-Crichlow, the Society of Surgical Oncology, The Knights of the York Cross of Honour and Borroughs Welcome.'
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.