Miriam Merad, MD, PhD
Researchers at The Tisch Cancer Institute have uncovered an intriguing mechanism that may help explain why radiation therapy eradicates cancerous tumors in some patients but not in others.
Their study, reported in the September 7, 2015, issue of Nature Immunology, examined how special skin immune cells, known as Langerhans cells, perform in mice models of melanoma.
They found that when skin that harbors tumors is exposed to ionizing radiation, Langerhans cells repair their affected DNA, making them resistant to radiotherapy. Langerhans cells exposed to radiation start to travel to nearby lymph nodes where they activate a population of regulatory T cells that inhibit antitumor immunity.
As a result, the tumor grows faster.
“Now that we better understand the mechanisms of how Langerhans cells impact the immune system, we can work, clinically, to deplete this cell population to promote antitumor immune response,” says lead author Jeremy Price, PhD, who is in his final year of medical school at the Icahn School of Medicine at Mount Sinai. “We’re helping to inform a very active field of research that’s developing around how to make treatments involving radiation and immunotherapy even more effective.”
Indeed, the identification of immune checkpoint inhibitors that enable the body to unleash a powerful anticancer response without being restrained by the cancerous tumors has been the most significant advance in cancer treatment in almost 40 years.
Jeremy Price, PhD
Miriam Merad, MD, PhD, Director of the Human Immune Monitoring Core at The Tisch Cancer Institute, and the study’s senior author, says the discovery of immune checkpoint inhibitors has given new impetus to her team’s work with Langerhans cells, which she initiated in 2002 as a postdoctoral student at Stanford University.
Dr. Merad says Mount Sinai’s study on melanoma can apply to other organs and types of cancer throughout the body, where cousins of Langerhans cells, known as macrophages, are also rendered immunosuppressive by radiotherapy. The new findings suggest that strategies aimed at depleting or activating Langerhans cells or macrophages prior to exposure to radiation therapy may synergize with checkpoint immunotherapy or targeted therapy to improve antitumor response.
Advances in cancer immunotherapy also are being led by Nina Bhardwaj, MD, PhD, Director of Immunotherapy, and Professor of Medicine (Hematology and Medical Oncology), at The Tisch Cancer Institute. In clinical studies, Dr. Bhardwaj and her team are exploring multiple approaches to immunotherapy, from intratumoral injections to the development of personalized vaccines used in combination with traditional treatments such as surgery, radiation, and chemotherapy.
The Tisch Cancer Institute, working in collaboration with researchers led by Eric E. Schadt, PhD, Director of the Icahn Institute for Genomics and Multiscale Biology, is one of a handful of U.S. medical institutions currently pursuing personalized vaccines. Dr. Schadt is also Chair of the Department of Genetics and Genomic Sciences, and the Jean C. and James W. Crystal Professor of Genomics.
In a unique, proof-of-concept study that will begin trials this year, Dr. Bhardwaj’s team will explore the feasibility of developing personalized vaccines for patients with multiple solid tumors.