Effect of miR-17 and miR-19a on TLR7 responses in primary CLL cells. (A) CLL cells were infected with lentiviruses expressing a scrambled vector control, the miR-17-92 cluster or antisense miR-17 and miR-19a. TNFA (upper panels) and TLR7 (lower panels) were measured by RT-PCR after 12 hours. Results for 4 patient samples are shown and indicate suppression of TLR7 and TNFA expression by miR-17 and miR-19a in primary leukemia cells. (B-C) Infected cells were treated with resiquimod (1 μg/ml) and mTNF-α and CD83 expression determined by flow cytometry after 4 hours. Numbers in the right upper quadrants indicate percentages of mTNF-α⁺CD83⁺ cells (B). Results for 4 patient samples are shown (C). Overexpression of miR-17-92 mimics the tolerizing effect of stromal factors and blockade of miR-17, miR-19a, or both, restores the responsiveness to TLR7-agonists in the presence of stromal factors. (D) Schematic diagram showing the effect of IL-6 on TLR7 signaling in a leukemia microenvironment. ***P < .05.