January 30, 2018
Native nano-vesicles and synthetic nano-particles: both can trigger an immune response that significantly reduces cancer metastasis—reports a NU team led by a CBC awardee, Shad Thaxton
Congratulations to Shad Thaxton, NU, and a graduate student in his lab, Michael Plebanek, for two recent publications in Nature Communications and Molecular Cancer Therapeutics. These papers explore the role of the immune system in preventing metastasis in cancer. Plebanek is first author on both publications. In 2014, Thaxton and a postdoc in his lab, Linda Foit, received a CBC Postdoctoral Research Award.
PhD Student Explores Role of Exosomes in Cancer Metastasis
Northwestern Medicine News Center | by Anna Williams | January 25, 2018
Northwestern Medicine scientists have demonstrated that tiny vesicles released from non-metastatic melanoma cells trigger an immune response that prevents the cancer from spreading throughout the body.
The vesicles, called 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, ’04 MD, ’07 PhD, associate professor of Urology. 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 they nurture an environment for incoming cancer cells.
In the current study, the Northwestern scientists wanted 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.”
Synthetic nanoparticles target immune response
In a separate study, Plebanek was also co-first author of a paper published last month in Molecular Cancer Therapeutics, together with Debayan Bhaumik, who is currently a medical student at Feinberg. The team showed that synthetic nanoparticles with surface features that mimic high-density lipoproteins (HDL) are able to specifically target and inhibit certain cells of the immune system, thereby activating an immune response against cancer. In mouse models, the nanoparticles significantly inhibited the spread and growth of cancer, and increased survival.
The findings may enable the development of new therapies and approaches for cancer that work by activating the patient’s own immune system, Thaxton said.
“Mike is a superb graduate student, who has made a number of important discoveries and published in high-impact journals by exploring how natural and synthetic nanoparticles interact with biological systems,” Thaxton said. “To some, embarking upon this endeavor seems intimidating, as it requires the development of a complex and broad intellectual framework along with a diverse technical skill set. Mike has always been up to the challenge.”
The Nature Communications paper was also co-authored by Nicholas Angeloni, PhD, director of strategic planning and coordination in the Office for Research and a former post-doctoral fellow in Thaxton’s laboratory; Stephen D. Miller, PhD, Judy Gugenheim Research Professor of Microbiology-Immunology and director of the Interdepartmental Immunobiology Center; and Igal Ifergan, PhD, research assistant professor of Microbiology-Immunology, among other Northwestern scientists.
The corresponding author of the paper, Olga Volpert, PhD, one of Plebanek’s co-advisors, is now an associate professor at the University of Texas MD Anderson Cancer Center.
The study was supported by National Cancer Institute (NCI) R01CA172669, and gift funds from Gibco—Life Technologies, NEI R24EY022883, Air Force Office of Scientific Research A9550-13-1-0192 and NCI R01CA167041, H. Foundation Stimulus Award, NCI R15 CA161634, the Robert H. Lurie Comprehensive Cancer Center, NIDDK 5T32DK062716 Cancer Center Support Grant NCI CA060553 for Flow Cytometry Core and the Northwestern Center for Advanced Microscopy/Nikon Imaging Facility.
The Molecular Cancer Therapeutics study was supported by the Air Force Office of Scientific Research grant FA95501310192; H Foundation NCI Stimulus Award from the Robert H. Lurie Comprehensive Center at Northwestern University; and grant funding from the National Cancer Institute (R01CA167041), as well as the Robert H. Lurie Comprehensive Cancer Center Flow Cytometry Core and the Northwestern University Center for Advanced Microscopy.
Plebanek MP, Angeloni NL, Vinokour E, Li J, Henkin A, Martinez-Marin D, Filleur S, Bhowmick R, Henkin J, Miller SD, Ifergan I, Lee Y, Osman I, Thaxton CS, Volpert OV. Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche. Nat Commun. 2017 Nov 6;8(1):1319. (PubMed)
Plebanek MP, Bhaumik D, Bryce PJ, Thaxton CS. Scavenger Receptor Type B1 and Lipoprotein Nanoparticle Inhibit Myeloid Derived Suppressor Cells. Mol Cancer Ther. 2017 Dec 27. [Epub ahead of print] (PubMed)
CBC Postdoctoral Research Award (2014):
PIs: Linda Foit and Colby Shad Thaxton (NU) for the project:
▸ Biomimetic, intrinsically therapeutic nanocarriers for targeted drug delivery in cancer