PTGES and neoplasm: Taken together, PTGES/PGE2 signaling plays two critical roles in lung metastasis: (i) the intrinsic role: PTGES/PGE2 signaling endows tumor cells resistant to T-cell cytotoxicity; and (ii) the extrinsic roles: PGE2 directly induces polarization of M2 macrophages, and through induction of cytokines/chemokines, such as G-CSF, PTGES/PGE2 signaling enhances MDSC recruitment, which inhibits T-cell cytotoxicity.