Figure 9. MNK inhibitors induce polarization of TAMs toward an M2 phenotype in ex vivo human PDAC slice cultures.

(A) Serial sections of human PDAC tumors (n = 15) were stained for Arginase-1 and phosphorylated eIF4E^S209 (p-eIF4E) by IHC. Scale bar: 200 μm. The staining positivity was analyzed by the TissueGnostics Imaging system using the HistoQuest, and the correlation analysis for Arginase-1 and p-eIF4E expression was performed using GraphPad. (B) Slice cultures (n = 1–4 replicates for each treatment group) from 6 different PDAC tumors were treated with DMSO (vehicle control) or CGP57380 for 5 days and stained for phosphorylated eIF4E (p-eIF4E), CD68, Arginase-1, CD163, MRC1, CD86, CD80, and MHCII. The percentage of positive cells, relative to the total number of nucleated cells, was analyzed by ImageJ. Scale bar: 50 μm. Data points represent individual patients. Paired t test was performed by GraphPad. *P < 0.05; **P < 0.01. (C) The relative expression of MKNK2, CD163, and MRC1 in TCGA studies and their transcript abundance from RNA-Seq data, quantified as RSEM, were downloaded from cBioPortal. Correlation analysis was performed in GraphPad to evaluate the relationship between MKNK2, CD163, and MRC1.