In summary, our data suggest that CMTM4 contributes to EGFR degradation and regulates its downstream mTOR/Akt/NF-κB signaling, which may regulate the production of inflammatory cytokines/chemokines (e.g., G-CSF) to recruit MDSCs and promote their immunosuppressive function in the tumor microenvironment. This evidence concerns the gene EGFR and neoplasm.