Researchers Discover Potential Boost to Immunotherapy
Mount Sinai researchers have discovered a pathway that regulates special immune system cells in lung cancer tumors, suppressing them and allowing tumors to grow. The scientists also figured out how to interrupt this pathway and ramp up the immune system to prevent tumor formation or growth, offering a potential boost to immunotherapy, according to a study published in Nature in March.
Researchers analyzed human and mouse lung cancer lesions, specifically studying the highly specialized immune cells called dendritic cells, which are considered the generals of the immune system. Dendritic cells give other immune system cells, called T-cells, identifying information from tumors so the T-cells can recognize and fight the cancer. Certain genetic material in the tumors, however, tamps down the dendritic cells’ function via this newly discovered immune regulatory pathway.
Scientists performed high-tech, single-cell sequencing and high-definition imaging on mouse and human tumors to study the dendritic cells’ activity in lung cancer and adjacent noncancerous lung tissues. They identified a molecular pathway that dampens dendritic cells’ ability to program T-cells to kill. This study also showed that reversing this pathway significantly improves tumor responses in animals.
Based on the findings, scientists are designing a clinical trial that they expect will enhance patients’ response to an immunotherapy called checkpoint blockade, by adding a second therapy that blocks the immune regulatory pathway that decreases dendritic cells’ function in tumors. Right now only about 20 percent of patients respond to checkpoint blockade therapies. The trial will be done in collaboration with Regeneron Inc.
“This study highlights the power of single-cell technologies to identify new therapeutic targets in cancer,” said senior author Miriam Merad, MD, PhD, Director of the Precision Immunology Institute and Mount Sinai Professor in Cancer Immunology at the Icahn School of Medicine at Mount Sinai, Co-leader of the Cancer Immunology Program at The Tisch Cancer Institute at Mount Sinai, and Director of the Mount Sinai Human Immune Monitoring Center.
About the Mount Sinai Health System
Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.
As a leading learning health system, Mount Sinai combines clinical expertise with scientific discovery to improve patient care while training the next generation of health care and biomedical leaders. The Health System provides care across every stage of life, from prenatal care through geriatrics, while advancing personalized medicine through artificial intelligence, data science, and biomedical research.
Mount Sinai is consistently recognized among the nation’s leading academic health systems for patient care, research, and education. The Mount Sinai Hospital is ranked No. 1 in New York by Newsweek and No. 5 on the magazine’s World’s Best Hospitals list. The Icahn School of Medicine at Mount Sinai ranks No. 11 among U.S. medical schools and No. 1 among freestanding medical schools for National Institutes of Health funding, reflecting the strength of its scientific enterprise and leadership in biomedical research.
