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Exosomes from Non-Metastatic Melanoma Can Stimulate Immune Response That Prevents Metastasis, Study Shows

Northwestern Medicine scientists have demonstrated that tiny vesicles (exosomes) released from non-metastatic melanoma cells trigger an immune response that prevents the cancer from spreading throughout the body. Michael Plebanek, a doctoral student in Feinberg’s Driskill Graduate Program in Life Sciences (DGP) at Northwestern Medicine, is the first author of the study, published on November 6, 2017 in Nature Communications. The open-access article is titled “Pre-Metastatic Cancer Exosomes Induce Immune Surveillance by Patrolling Monocytes at the Metastatic Niche.” Exosomes are nano-sized delivery vehicles that are released by cells into the bloodstream. In recent years, significant research has focused on the role of exosomes released by cancer cells in promoting the spread of cancer. This study, however, is the first to demonstrate that exosomes can also suppress metastasis, depending on the state of the cancer cell. “Mike’s paper is important because it provides data on the mechanisms by which these natural nanovesicles enhance the ability of the immune system to clear tumor cells and prevent cancer from spreading,” said C. Shad Thaxton, MD, PhD, Associate Professor of Urology and a co-author of the Nature Communications paper. Dr. Thaxton is also Plebanek’s advisor and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “Because the spread of cancer cells throughout the body is devastating for cancer patients, developing a deeper understanding of the process is critically important and adds to the knowledge that may result in new treatments.” Previously, it had been established that exosomes released from highly metastatic tumor cells support the spread of cancer by traveling to other organs in the body, where the exosomes nurture an environment for incoming cancer cells. In the current study, the Northwestern scientists sought to understand the role of exosomes from tumors that had not progressed to metastasis. Using animal models of melanoma, they discovered that the non-metastatic exosomes actually suppressed metastasis to the lung, by stimulating an immune response that helps to eliminate tumor cells. Specifically, the scientists showed that pre-metastatic exosomes carry a protein called PEDF which ramps up the production of patrolling monocytes — immune cells that crawl along blood vessels, clearing metastasizing melanoma cells along the way. Exosomes in samples taken from patients with non-metastatic melanomas also supported the results. The authors noted that the study’s findings have the potential to inform future development of novel cancer therapies and delivery methods. “We could now identify other biomolecules in these exosomes that increase immune surveillance and prevent metastasis — such as PEDF — and possibly develop them into cancer therapies in the future,” Plebanek explained. “There’s also a nanotechnology avenue. One of the biggest opportunities with exosomes is that they are nano-sized delivery vehicles, and we could utilize the knowledge we’ve gained about the targeting properties of these exosomes.”

[Press release] [Nature Communications article]