Prostaglandin E₂ pathway in colonic macrophage

The "Colonic macrophage PGE₂ pathway" encompasses the synthesis and signaling of prostaglandin E₂ (PGE₂) by enzymes such as cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) in colonic macrophages. This pathway modulates immune responses, inflammation, macrophage polarization, tumor immune evasion, and intestinal motility. It promotes the polarization of macrophages to an immune-suppressive (M2-like) phenotype, inhibits anti-tumor immunity (notably by inducing checkpoint molecules like PD-1 on macrophages and T cells via EP4 signaling), and stimulates colorectal tumor growth and metastasis. The pathway is implicated in poor prognosis in colorectal cancer and is targeted therapeutically by COX-2 inhibitors and EP receptor antagonists, although these drugs have important safety considerations.

Other names

COX-2–PGE₂ pathway in macrophagesProstaglandin E2 signaling in colonic macrophage

Inhibition of COX-2 limits PGE₂ production, reducing immune suppression and tumor progression Antagonism of EP receptors (especially EP4) blocks PGE₂-mediated immunosuppression and tumor-promoting signaling