Combining SHP2 inhibition with CX3CR1 inhibition shrinks tumors and normalizes the tumor microenvironment

NF1 loss increases RAS-MAPK signaling in myeloid cell dominant benign nerve tumors that cause significant clinical burden, in which MEK inhibitor therapy is only partially effective. We studied SHP2 inhibition, which targets RAS-MAPK and has additional immunomodulatory effects, in a validated preclinical model system and found that both MEK and SHP inhibitors shrank tumor volume and tumor immune compartments. However, neither inhibitor was durable or efficacious in all mice. To identify druggable targets, paraspinal tumors from mice treated for 30 days with either vehicle, MEK inhibitor, or SHP2 inhibitor were collected, dissociated to achieve single-cell suspension and transcriptionally profiled.