Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche

Nature Communications
Michael P PlebanekOlga V Volpert

Abstract

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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Datasets Mentioned

BETA
GM130

Methods Mentioned

BETA
transmission electron microscopy
Flow cytometry
FACS
ELISA
Protein assay
dynamic light scattering
Flow
FCS
electrophoresis
Assay

Software Mentioned

AxioVision
ImageJ
Nikon Elements
GraphPad Prism
FCS Express

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