Tumor-Derived Exosomes Contain microRNAs with Immunological Function: Implications for a Novel Immunosuppression Mechanism
Damiano M. Cereghetti and Peter P. Lee
Affiliation: Department of Cancer Immunotherapeutics & Tumor Immunology (CITI), City of Hope and Beckman Research Institute, Beckman Center, room 5109, 1500 East Duarte Road, Duarte, CA 91010, USA.
Tumor-derived vesicles (TDV) have been recently implicated in immunosuppression by transporting specific
proteins, including Fas ligand (FasL) and TRAIL, to immune cells. We hypothesized that TDVs carrying miRNAs with
immunological function could interfere with the translational machinery of immune cells and lead to TDV-mediated immunosuppression
in cancer. We show that TDVs from human tumor cells indeed contain multiple miRNA species with
known roles in lymphocyte development and function: hsa-miR-146a, miR-29a, and miR-21. Quantification by RT-PCR
shows that the amount of miR-21 within TDVs isolated from the breast cancer cell line HCC1806 is at physiologically
relevant levels. Additionally, we show that these miRNAs carried by TDVs copurify with argonaute proteins. This observation
corroborates the idea that the machinery of microvesicle secretion and that of RNA interference are interconnected.
Keywords: Cancer immunosuppression, exosomes, microRNA, tumor microenvironment.
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