BOSTON, MA—Researchers from Brigham and Women's Hospital (BWH) have made a groundbreaking discovery that will shape the future of melanoma therapy. The team, led by Thomas S. Kupper, MD, chair of the BWH Department of Dermatology, and Rahul Purwar, PhD, found that high expression of a cell-signaling molecule, known as interleukin-9, in immune cells inhibits melanoma growth.
Their findings will be published online in the July 8, 2012 issue of Nature Medicine.
After observing mice without genes responsible for development of an immune cell called T helper cell 17 (TH17), researchers found that these mice had significant resistance to melanoma tumor growth, suggesting that blockade of the TH17 cell pathway favored tumor inhibition. The researchers also noticed that the mice expressed high amounts of interleukin-9.
"These were unexpected results, which led us to examine a possible contribution of interleukin-9 to cancer growth suppression." said Purwar.
The researchers next treated melanoma-bearing mice with T helper cell 9 (TH9), an immune cell that produces interleukin-9. They saw that these mice also had a profound resistance to melanoma growth. This is the first reported finding showing an anti-tumor effect of TH9 cells.
Moreover, the researchers were able to detect TH9 cells in both normal human blood and skin, specifically in skin-resident memory T cells and memory T cells in peripheral blood mononuclear cells. In contrast, TH9 cells were either absent or present at very low levels in human melanoma. This new finding paves the way for future studies that will assess the role of interleukin-9 and TH9 cells in human cancer therapy.
"Immunotherapy of cancer is coming of age, and there have been exciting recent results in patients with melanoma treated with drugs that stimulate the immune system," said Kupper. "We hope that our results will also translate to the treatment of melanoma patients, but much work still needs to be done."
According to the researchers, other cell-signaling molecules have been used in treating melanoma; however, this study is the first to investigate the role of interleukin-9 in melanoma tumor immunity.
Melanoma is the most dangerous form of skin cancer. The National Cancer Institute estimates that in 2012, there will be more than 76,000 new cases of melanoma in the United States and 9,180 deaths. Melanoma is curable if recognized and treated early.
This research was supported by the United States National Institutes of Health (R01 AI-41707, R01 AI-097128, P50 CA-093683, R01-AR-056720, R03-MH-095529 and Z01-ES-101586) and The Skin Cancer Foundation.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs nearly 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving nearly 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $625 million in funding. BWH continually pushes the boundaries of medicine, including building on its legacy in organ transplantation by performing the first face transplants in the U.S. in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies, OurGenes and the Women's Health Initiative. For more information and resources, please visit BWH's online newsroom.
Journal
Nature Medicine