Mount Sinai researchers have discovered a pathway that regulates special immune system cells in lung cancer tumours, suppressing them and allowing tumours to grow.
The scientists also figured out how to interrupt this pathway and ramp up the immune system to prevent tumour formation or growth, offering a potential boost to immunotherapy, according to a study published in Nature.
Researchers analysed human and mouse lung cancer lesions, specifically studying the highly specialised 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 tumours so the T-cells can recognise and fight the cancer.
Certain genetic material in the tumours, 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 tumours 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 tumour 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 tumours.
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.
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