Myeloid-specific SHP-2 ablation alters the fate commitment of myeloid cells and induces anti-tumor immunity

We generated mice with conditional targeting of the Ptpn11 gene (encoding for Shp-2) in T cells (Shp-2fl/flLckCre) or myeloid cells (Shp-2fl/flLysMCre). Although no difference in tumor growth was observed between Shp-2fl/flLckCre and control mice and both groups were similarly benefitted by PD-1 blockade, Shp-2fl/flLysMCre mice had significantly diminished tumor growth that was not further decreased by anti-PD-1 treatment. As revealed by RNA-seq, myeloid-specific Shp-2 ablation was paralleled by expansion of activated myeloid cells and macrophages with molecular signatures of enhanced neutrophil and macrophage differentiation, phagocytosis, antigen-presenting function, TLR and type I IFN signaling, chemokine production, and expression of immunostimulatory molecules, which promoted T cell recruitment and activation. Control Shp-2fl/fl and Shp-2fl/flLysMCre mice were inplanted with M17 tumors and 15 days later GR-1+ MDSC were collected from the spleen, and CD11b+F4/80+ TAMs were collected from the tumor site. RNA was extracted and differential gene expression was examined by RNAsequencing. Two replicates of RNA samples isolated from GR1+ MDSC per experimental group were analyzed. Three replicates of RNA samples isolated from TAMs per experimental group were analyzed.