Fig. 4: HLA-E expression is modulated by anti-MM drugs.
From: CREB1 promotes expression of immune checkpoint HLA-E leading to immune escape in multiple myeloma
A HLA-E mRNA fold change in OPM-2 and H929 cells treated with DMSO, lenalidomide (LEN) 1 μM for 72 h, pomalidomide (POM) 1 μM for 72 h, and panobinostat (PANO) 100 nM for 24 h. n = 2, t test, two-tailed. OPM-2: DMSO versus LEN p = 0.0149, *; DMSO versus POM p = 0.0293, *; DMSO versus PANO p = 0.05, *. H929: DMSO versus LEN p = 0.0349, *; DMSO versus POM p = 0.0063, **; DMSO versus PANO p = 0.0002, ***. B HLA-E MFI fold change in OPM-2 cells and H929 cells treated with DMSO, LEN 1 μM for 72 h, POM 1 μM for 72 h, and PANO 100 nM for 24 h. n = 3, t test, two-tailed. OPM-2: DMSO versus LEN p < 0.0001, ****; DMSO versus POM p = 0.0021, **; DMSO versus PANO p = 0.0105, *. H929: DMSO versus LEN p = 0.0004, ***; DMSO versus POM p = 0.0075, **; PANO p = 0.97, ns. C HLA-E MFI fold change in OPM-2 cells treated with DMSO, LEN 0.1 μM, or POM 0.1 μM for 4 and 7 days. n = 2, t test, two-tailed. Day 4: DMSO versus LEN p = 0.05, *; DMSO versus POM p = 0.0115, *; day 7: DMSO versus LEN p = 0.0255, *; DMSO versus POM p = 0.0313, *. D HLA-E MFI fold change in OPM-2 cells and MM patient samples treated with DMSO, POM 1 μM, 666-15 (CREBi) 0.3 μM, or POM + CREBi. OPM-2: OPM-2 cells were treated for 72 h. n = 2, t test, two-tailed; POM versus POM + CREBi p = 0.0018, **. MM patients: patient samples were treated for 48 h. n = 3, t test, two-tailed; POM versus POM + CREBi p = 0.0059, **. E Gene-expression profiling for HLA-E in n = 16 relapsed refractory patients with MM with matched pre- and post-lenalidomide (LEN) data from dataset GSE8546. F Western blot analysis for p-CREB1, STAT1, and GAPDH in OPM-2, H929, and MM.1S cells treated with DMSO and POM 1 μM for 6, 24, and 48 h.
