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Page 36 Extracell Vesicles Circ Nucleic Acids 2020;1:20-56 I http://dx.doi.org/10.20517/evcna.2020.10

20. Immunoregulatory properties of cancer stem cell derived extracellular vesicles

Authors: Jordan Pavlic, Joehleen Archard, Jan Nolta, Johnathon D. Anderson
E-mail: jordanpavlic@csus.edu
Affiliations:
Stem Cell Program &Institute for Regenerative Cures University of California Davis Health Systems, University
of California Davis, Sacramento, CA, USA.
Department of Biological Sciences, California State University, Sacramento, CA, USA.
Department of Otolaryngology University of California Davis Health Systems, California Institute for
Regenerative Medicine, University of California Davis, Sacramento, CA, USA.
Abstracts: Head and neck squamous cell carcinoma (HNSCC) is the 6th most common malignancy
globally, and the five year survival rate for stage III and IV patients is only 50%. HNSCC patients who
relapse have a mean survival rate of less than one year. As such, understanding the mechanism of local
recurrences and their immunoevasive properties is imperative to improving disease outcomes for stage III
and IV HNSCC patients. Cancer stem cells (CSCs) are a subpopulation of cells within a tumor that possess
self-renewing properties that have been linked to tumor initiation, neoplastic maintenance, and recurrence
post treatment. Residual CSCs not eliminated by surgical resection, or chemoradiation, are thought to
induce recurrence in many patients. A key feature of CSCs is their immunoregulatory properties that allow
them to evade immunosurveillance and elimination. Several studies have established that CSCs secrete
canonical secretory proteins with immunoregulatory properties, however, it remains unclear what role,
if any, extracellular vesicles play in CSCs immunomodulatory properties. Using a co-culture system and
multichromatic flow cytometry analysis we have evaluated CSCs and their derived EVs ability to regulate
the polarization of the monocyte cell line, THP-1 macrophages towards an M2-like immunosuppressive
phenotype. We have also analyzed the expression patterns of inhibitory immune checkpoint receptors
and glycan factors in CSCs and CSC-EVs. Our preliminary data suggests that CSCs and CSC-EVs express
numerous immune checkpoint proteins and associated glycans such as sialic acid residues. Our data also
suggests that CSC-EVs induce M2-like polarization of macrophages.

21. Extracellular vesicles in diabetes mellitus carry inflammatory cargo that affects cellular
behavior

1,3
1
1,2
1
Authors: Nicole Noren Hooten , Sharon F. Wu , David W. Freeman , Nicolle A. Mode , Alan B.
1
Zonderman , Michele K. Evans 1
E-mail: norenhootenn@mail.nih.gov
Affiliations:
1 Laboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health,
Baltimore, MD, USA.
2 Kansas City University of Medicine and Biosciences, Kansas City, MO, USA.
3 University of Utah School of Medicine, Salt Lake City, UT, USA.
Abstracts: Type 2 diabetes mellitus is a global health problem evidenced by its rising prevalence and
incidence worldwide. This chronic metabolic disease causes multiple end organ complications including
inflammation-related atherosclerotic peripheral vascular disease, which results in devastating morbidity
and mortality. Previously, we reported that individuals with diabetes mellitus have higher levels of
circulating extracellular vesicles (EVs). EVs from diabetic individuals are more readily internalized by
monocytes and induce inflammatory signals in these cells. To further elucidate the molecular cargo that
may elicit these responses in cells, we quantified inflammatory protein levels in plasma-derived EVs from