PLX277949

GSE76356: DICER controls macrophage polarization and tumor response to immunotherapy

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Tumor-associated macrophages (TAMs) have immunosuppressive capacity in mouse models of cancer. Here we show that the genetic deletion of the microRNA (miRNA)-processing enzyme DICER in TAMs broadly programs them to a CD11c+MRC1/low M1-like immunostimulatory phenotype characterized by activated interferon- (IFN-)/STAT1/IRF signaling. M1-like TAM programming fostered the recruitment of cytotoxic T-cells (CTLs), including tumor-antigen-specific CTLs, inhibited tumor growth, and enhanced the efficacy of PD1 checkpoint blockade. Bioinformatics analysis of TAM transcriptomes identified a limited set of miRNAs putatively involved in TAM programming. Re-expression of Let-7 in Dicer-deficient TAMs was sufficient to partly rescue the M2-like (protumoral) TAM phenotype and abate tumor CTL infiltration. Targeted suppression of DICER activity in TAMs may, therefore, stimulate antitumor immunity and enhance the efficacy of cancer immunotherapy. SOURCE: Chia-Huey Ooi (chia-huey.ooi@roche.com) - F. Hoffmann-La Roche Ltd.