GMPS (guanosine monophosphate synthase) catalyzes the final committed step of GMP biosynthesis, converting xanthine monophosphate to GMP in the presence of glutamine and ATP. This essential purine nucleotide biosynthetic enzyme functions in the cytosol and is critical for nucleotide availability in rapidly dividing cells. Beyond classical nucleotide metabolism, GMPS has emerged as a key regulator of immune evasion in cancer. In hepatocellular carcinoma, GMPS increases PD-L1 expression by facilitating its glycosylation modification through enhanced interaction with STT3A, an oligosaccharyltransferase subunit 1. This post-translational modification of PD-L1 impairs CD8+ T cell tumor-killing capacity, enabling immune escape. Importantly, GMPS inhibition with angustmycin A suppresses PD-L1 expression, reduces tumor growth, and enhances anti-CTLA-4 immunotherapy efficacy 1. GMPS expression is notably elevated in myeloid progenitor compartments. Granulocyte-monocyte progenitors (GMPs) represent a critical population in both normal hematopoiesis and tumor-induced systemic immunosuppression 2, 3. GMPs show heterogeneity with distinct lineage potential, differentiating into neutrophils and monocytes through transcriptionally and epigenetically distinct pathways 4, 5. Therapeutically, GMPS represents a promising immunotherapeutic target, as its inhibition simultaneously reduces PD-L1-mediated immune suppression and may limit myeloid-derived suppressor cell expansion in tumors.