Saliva exosomes from pancreatic tumor–bearing mice modulate NK cell phenotype and antitumor cytotoxicity

ABSTRACT Tumor exosomes are emerging as antitumor immunity regulators; however, their effects on secondary exosome secretion by distal organs have not been explored. We have previously demonstrated that suppression of exosomes at the distal tumor site of pancreatic ductal adenocarcinoma (PDAC) ablat...

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Bibliographic Details
Published in:The FASEB journal 2017-03, Vol.31 (3), p.998-1010
Main Authors: Katsiougiannis, Stergios, Chia, David, Kim, Yong, Singh, Ram P., Wong, David T. W.
Format: Article
Language:English
Subjects:
Adenocarcinoma
Animals
Antitumor activity
Bearing
Biomarkers
Biosynthesis
cancer
Carcinoma, Pancreatic Ductal - immunology
Cell Line, Tumor
Cytotoxicity
Cytotoxicity, Immunologic
Exosomes
Exosomes - immunology
extracellular vesicles
Female
immune surveillance
Immunity
Immunologic Factors - metabolism
Immunoregulation
Immunosurveillance
Killer Cells, Natural - immunology
Mice
Mice, Inbred C57BL
Natural killer cells
Organs
Pancreas
Pancreatic Neoplasms - immunology
Phenotype
Regulators
Saliva
Saliva - immunology
Toxicity
Tumor cells
Tumors
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Summary:ABSTRACT Tumor exosomes are emerging as antitumor immunity regulators; however, their effects on secondary exosome secretion by distal organs have not been explored. We have previously demonstrated that suppression of exosomes at the distal tumor site of pancreatic ductal adenocarcinoma (PDAC) ablated the development of salivary biomarker profile. Here, we explore the function of salivary exosomes from tumor‐bearing mice in immune surveillance. We provide evidence that salivary exosomes from mice with PDAC exhibit a suppressive effect that results in reduced tumor‐killing capacity by NK cells. Salivary exosomes from mice with PDAC where pancreatic tumors were engineered to suppress exosome biogenesis failed to suppress NK cell cytotoxic potential against tumor cells, as opposed to salivary exosomes from mice with PDAC with normal tumor exosome biogenesis. These results reveal an important and previously unknown mechanism of antitumor immune regulation and provide new insights into our understanding of the alterations of this biofluid during tumor development.—Katsiougiannis, S., Chia, D., Kim, Y., Singh, R. P., Wong, D. T. W. Saliva exosomes from pancreatic tumor‐bearing mice modulate NK cell phenotype and antitumor cytotoxicity. FASEB J. 31, 998–1010 (2017). www.fasebj.org
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.201600984R