Fig. 5

Trabectedin effects on MM recognition by innate immune system effectors. a On the left, expression levels of all known ligands of NK activating receptors derived from the results of the GEP of U266 treated with 2.5 nM of trabectedin. On the right, overlay histograms (scattered plots) underlying the modulation in MICA/B and ULBP1 expression in OPM2, U266, and MM1S, after trabectedin treatment. b Representative dot plot (of 3 different experiments) reporting the % of CD107a NK-92 after co-culture with different MM cells exposed to PBS or to 0.25 nM (MM1S), 1 nM (OPM-2), or 2.5 nM (U266) of trabectedin. c In the upper part, expression levels of negative or positive regulators of MICA/B derived from the results of the GEP of U266 treated with 2.5 nM of trabectedin. In the lower part, Western blot data showing protein expression of the previously identified MICA/B regulators: IKZF1, IRF4, and E2F1; the densitometric analysis of Western blot was performed on the triplicate blots for IKZF1 and E2F1 in both cell lines. d Sequences of miRNA families predicted to target at the same time the 3′UTR regions of MICA, MICB, and E2F1 (all upregulated after trabectedin treatment). These miRNAs present AAGUGC that interact with UUCACG motif of 3′UTR regions of previously reported genes. e Histograms reporting the expression of miR-17 and miR-20a in U266 and OPM2 cells untreated or exposed to 2.5 nM and 1 nM of trabectedin, respectively. f Overlay histogram reporting MICA/B expression in EV-U266 and 17-92-U266 cells alone or after treatment with 2.5 nM of trabectedin. On the right, histograms reporting the MFI of MICA/B of three different replicates. g Histograms showing apoptosis levels in EV-U266 as compared to 17-92-U266 after trabectedin treatment with 2.5 nM. h Cartoon representing the pleiotropic activity of trabectedin in MM, including direct cytotoxicity of trabectedin on MM cells, immune-modification of cytotoxicity on MM cells, and reduction of angiogenesis. *p < 0.05