Botta, CCucè, MPitari, M RCaracciolo, DGullà, AMorelli, ERiillo, CBiamonte, LGallo Cantafio, M EPrabhala, RMignogna, CDi Vito, AAltomare, EAmodio, NDi Martino, M TCorreale, PRossi, MGiordano, AMunshi, N CTagliaferri, PTassone, P2018-05-302018Botta, C., M. Cucè, M. R. Pitari, D. Caracciolo, A. Gullà, E. Morelli, C. Riillo, et al. 2018. “MiR-29b antagonizes the pro-inflammatory tumor-promoting activity of multiple myeloma-educated dendritic cells.” Leukemia 32 (4): 1003-1015. doi:10.1038/leu.2017.336. http://dx.doi.org/10.1038/leu.2017.336.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37067730Dendritic 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-κB, 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.en-USJournal Article2018-05-3010.1038/leu.2017.336