Myeloid-specific ablation of Pdcd1 alters fate comittment of tumor-associated macrophages and induces anti-tumor immunity

We generated mice with conditional targeting of the Pdcd1 gene (encoding for PD-1) in myeloid cells (Pdcd1-2fl/flLysMCre). Pdcd1-2fl/flLysMCre mice had significantly diminished tumor growth. As revealed by RNA-seq, myeloid-specific Pdcd1 ablation was paralleled by generation of myeloid cells with monocytic dominance, and activated macrophages with molecular signatures of enhanced myeloid cell differentiation, macrophage activation, phagocytosis, TLR and NF-kB signaling, chemokine and cytokine production, and expression of immunostimulatory molecules. Overall design: Control Pdcd1fl/fl and Pdcd1fl/flLysMCre mice were inplanted with M17 tumors and 15 days later CD11b+F4/80+ TAMs were collected from the tumor site. RNA was extracted and differential gene expression was examined by RNAsequencing. Three replicates of RNA samples isolated from TAMs per experimental group were analyzed.