In an immunogenic syngeneic preclinical cancer model, SHP2 inhibition drove direct and selective depletion of pro-tumorigenic macrophages via attenuation of CSF1 receptor signaling and increased antitumorigenic macrophages via a mechanism independent of CD8+ T cells or IFNγ (Quintana et al, 2020). The gene discussed is PTPN11; the disease is cancer.