Loading...
MIR-29b antagonizes the pro-inflammatory tumor-promoting activity of multiple myeloma-educated dendritic cells
Botta, C Cucè, M Pitari, MR Caracciolo, D Gullà, A Morelli, E Riillo, C Biamonte, L Gallo Cantafio, ME Prabhala, R
Botta, C
Cucè, M
Pitari, MR
Caracciolo, D
Gullà, A
Morelli, E
Riillo, C
Biamonte, L
Gallo Cantafio, ME
Prabhala, R
Citations
Altmetric:
Genre
Journal Article
Date
2018-04-01
Advisor
Committee member
Group
Department
Permanent link to this record
Collections
Research Projects
Organizational Units
Journal Issue
DOI
10.1038/leu.2017.336
Abstract
© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Dendritic cells (DCs) have a key role in regulating tumor immunity, tumor cell growth and drug resistance. We hypothesized that multiple myeloma (MM) cells might recruit and reprogram DCs to a tumor-permissive phenotype by changes within their microRNA (miRNA) network. By analyzing six different miRNA-profiling data sets, miR-29b was identified as the only miRNA upregulated in normal mature DCs and significantly downregulated in tumor-associated DCs. This finding was validated in primary DCs co-cultured in vitro with MM cell lines and in primary bone marrow DCs from MM patients. In DCs co-cultured with MM cells, enforced expression of miR-29b counteracted pro-inflammatory pathways, including signal transducer and activator of transcription 3 and nuclear factor-κ B, and cytokine/chemokine signaling networks, which correlated with patients' adverse prognosis and development of bone disease. Moreover, miR-29b downregulated interleukin-23 in vitro and in the SCID-synth-hu in vivo model, and antagonized a Th17 inflammatory response. All together, these effects translated into strong anti-proliferative activity and reduction of genomic instability of MM cells. Our study demonstrates that MM reprograms the DCs functional phenotype by downregulating miR-29b whose reconstitution impairs DCs ability to sustain MM cell growth and survival. These results underscore miR-29b as an innovative and attractive candidate for miRNA-based immune therapy of MM.
Description
Citation
Citation to related work
Springer Science and Business Media LLC
Has part
Leukemia
ADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu