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Saliva exosomes from pancreatic tumor–bearing mice modulate NK cell phenotype and antitumor cytotoxicity
Author(s) -
Katsiougiannis Stergios,
Chia David,
Kim Yong,
Singh Ram P.,
Wong David T. W.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600984r
Subject(s) - microvesicles , exosome , cancer research , immune system , cytotoxicity , cytotoxic t cell , biology , pancreatic cancer , tumor microenvironment , immunology , cancer , in vitro , microrna , biochemistry , gene , genetics
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