Treatment with miR-146b-5p mimic inhibits CLL growth, proliferation, and IL-12Rβ1 expression in the NSG mouse model. (A) Low magnification image (top) of longitudinal sections of paraffin-embedded mouse spleen (CLL GE1-PM129) stained for CD20 (left) or CD3 (right). The spleen from a mouse treated with miR CTR mimic (NSG13, top) or with miR-146b-5p mimic (NSG16, bottom) is represented. (B) Higher magnification (40×) of the areas of spleen highlighted by the boxes in (A) showing a decrease of neoplastic B cells (and not of T cells) in the follicular infiltrates after treatment with miR-146b-5p compared with control samples. (C) IHC analysis of Ki67⁺ cycling cells at 100× and 200× magnification in spleens of the same mice treated as indicated in (A). Decreased proliferating cells in the spleen infiltrate of mice treated with miR-146b-5p mimic (lower panels) compared with control samples (upper panels) is evident. (D) High magnification image (400×) of longitudinal sections of the spleens of the same mice as in (C) double-stained for CD20 and Ki67. (E) Double-marker immunofluorescence (IF) and confocal microscopy (high-magnification image 400×) analysis of IL-12Rβ1 chain and CD20 (upper panels) or CD3 chain (lower panels) and DAPI of the spleens of miR-CTR (NSG 14, left) or miR-146b-5p mimic-treated mice (NSG 5, right). (F) Double-marker IF and confocal microscopy (high-magnification 200×) analysis of IL-12Rβ1 chain and IL-23 or DAPI of a representative of the spleens of miR-CTR (NSG 14, upper panel) or miR-146b-5p mimic-treated mice (NSG 5, lower panel). IF microphotographs are representative of analyses of ≥5 low-power magnification (100×) or 10 high-power magnification (200× and 400×) microscopic fields performed on each mouse tissue sample.