TY - JOUR
T1 - Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche
AU - Plebanek, Michael P.
AU - Angeloni, Nicholas L.
AU - Vinokour, Elena
AU - Li, Jia
AU - Henkin, Anna
AU - Martinez-Marin, Dalia
AU - Filleur, Stephanie
AU - Bhowmick, Reshma
AU - Henkin, Jack
AU - Miller, Stephen D.
AU - Ifergan, Igal
AU - Lee, Yesung
AU - Osman, Iman
AU - Thaxton, C. Shad
AU - Volpert, Olga V.
N1 - Funding Information:
This work was supported by the following funds: NCI R01CA172669, and a gift funds from Gibco—Life Technologies (O.V.V.); NEI R24EY022883 (O.V.V. and J.H.); Air Force Office of Scientific Research A9550-13-1-0192 and NCI R01CA167041 (C.S.T.); H. Foundation Stimulus Award (O.V.V. and C.S.T.), NCI R15 CA161634 (S.F.), Robert H. Lurie Comprehensive Cancer Center (M.P.P.), NIDDK 5T32DK062716 (N.L.A.) Cancer Center Support Grant NCI CA060553 for Flow Cytometry Core and the Northwestern Center for Advanced Microscopy/Nikon Imaging Facility.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Metastatic cancers produce exosomes that condition pre-metastatic niches in remote microenvironments to favor metastasis. In contrast, here we show that exosomes from poorly metastatic melanoma cells can potently inhibit metastasis to the lung. These "non-metastatic" exosomes stimulate an innate immune response through the expansion of Ly6Clow patrolling monocytes (PMo) in the bone marrow, which then cause cancer cell clearance at the pre-metastatic niche, via the recruitment of NK cells and TRAIL-dependent killing of melanoma cells by macrophages. These events require the induction of the Nr4a1 transcription factor and are dependent on pigment epithelium-derived factor (PEDF) on the outer surface of exosomes. Importantly, exosomes isolated from patients with non-metastatic primary melanomas have a similar ability to suppress lung metastasis. This study thus demonstrates that pre-metastatic tumors produce exosomes, which elicit a broad range of PMo-reliant innate immune responses via trigger(s) of immune surveillance, causing cancer cell clearance at the pre-metastatic niche.
AB - Metastatic cancers produce exosomes that condition pre-metastatic niches in remote microenvironments to favor metastasis. In contrast, here we show that exosomes from poorly metastatic melanoma cells can potently inhibit metastasis to the lung. These "non-metastatic" exosomes stimulate an innate immune response through the expansion of Ly6Clow patrolling monocytes (PMo) in the bone marrow, which then cause cancer cell clearance at the pre-metastatic niche, via the recruitment of NK cells and TRAIL-dependent killing of melanoma cells by macrophages. These events require the induction of the Nr4a1 transcription factor and are dependent on pigment epithelium-derived factor (PEDF) on the outer surface of exosomes. Importantly, exosomes isolated from patients with non-metastatic primary melanomas have a similar ability to suppress lung metastasis. This study thus demonstrates that pre-metastatic tumors produce exosomes, which elicit a broad range of PMo-reliant innate immune responses via trigger(s) of immune surveillance, causing cancer cell clearance at the pre-metastatic niche.
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U2 - 10.1038/s41467-017-01433-3
DO - 10.1038/s41467-017-01433-3
M3 - Article
C2 - 29105655
AN - SCOPUS:85032961873
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1319
ER -
