PTGER2 (prostaglandin E receptor 2) is a G protein-coupled receptor that mediates prostaglandin E2 (PGE2) signaling through Gs protein-activation of adenylate cyclase and increased intracellular cAMP 1. The receptor functions as a key immune regulator in the tumor microenvironment, where elevated PGE2 concentrations suppress anti-tumor immunity. In CD8+ tumor-infiltrating lymphocytes, PTGER2 (along with EP4) blocks IL-2 sensing by downregulating IL-2Rγc, impairing mTOR signaling, oxidative phosphorylation, and T cell expansion 23. Similarly, PTGER2 activation in macrophages downregulates c-Myc and oxidative metabolism, shifting M1-like macrophages toward an anti-inflammatory state 3. PTGER2 is upregulated in mature polymorphonuclear myeloid-derived suppressor cells from cancer patients and serves as a differentiation marker 4. Beyond immunity, PTGER2 expression predicts poor prognosis in ovarian cancer through METTL3-mediated m6A modification, enhancing cancer stemness, chemoresistance, and metastasis 5. In gastric cancer, high PTGER2 expression in CD8+ T cells correlates with worse prognosis 6. PTGER2 signaling can be modulated by GPRC5B, which facilitates EP2-mediated cAMP signaling in macrophages 7. Together, these findings establish PTGER2 as a critical immunosuppressive node in tumor microenvironments and a potential therapeutic target for cancer immunotherapy.