Phenotypic skewing of tumor-associated macrophages by cooperative actions of IL-6 and IL-4 in IFN-stimulated differentiating monocytes

I IFNs promote differentiating monocytes to differentiate into tumor-associated macrophages (TAMs) and limit the I IFNs anti-tumor effects.But how macrophage polarization is shaped by complex signals in the tumor microenvironment during IFN therapies is incompletely understood. Herein, it was discovered that I IFNs could stimulate transitional monocytes to secrete interleukins IL-4 and IL-6, which interact to influence target genes expression in primary mouse bone-marrow-derived macrophages (BMDMs). To analyze the synergism mechanism, RNA seq was performed. Bone marrow derived macrophages were cultured under the 20ng/ml M-CSF for 7days, and treated with the indicated cytokine, samples were harvested for total RNAs and subjected to RNA sequencing analyses. BMDMs were stimulated with individual or combinatorial cytokines (IL-4 10 ng/ml, IL-4 10ng/ml+IL-6 40 ng/ml, IL-13 40 ng/ml, IL-13 40ng/ml+IL-6 40ng/ml) for 24 h,. each sample had three replicates. Total RNA was harvested at the indicated time, and then the RNA samples were subjected to RNA sequencing analyses.