Tumor-Derived Exosomes Contain microRNAs with Immunological Function: Implications for a Novel Immunosuppression Mechanism
Damiano M. Cereghetti and Peter P. LeeAffiliation:
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.
AbstractTumor-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.
Cancer immunosuppression, exosomes, microRNA, tumor microenvironment.
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