Prostaglandins in cancer revisited: principles of production, mechanisms of immune regulation, and therapeutic perspectives

ABSTRACT: The cyclooxygenase (COX) signaling pathway is frequently dysregulated in cancer, resulting in the aberrant production of prostaglandins, a distinct class of bioactive lipids with immunoregulatory functions. One of these factors, prostaglandin E2 (PGE2), has over the years emerged as a predominant COX-derived factor in tumors, with numerous studies exploring its downstream signaling and functional impact across diverse cell types. Recent studies have substantially advanced our understanding of how PGE2 promotes cancer immune evasion through its deleterious effects on tumor-infiltrating immune cells. Here, we summarize some key principles of PGE2-mediated immune regulation in tumors, focusing on the current knowledge of PGE2 production mechanisms and recent advances in our understanding of molecular features and functional consequences of PGE2 signaling in innate and adaptive immune cells. We further discuss how strategies aimed at disrupting the local activity of prostaglandins in tumors, or interfering with the distinct molecular features characteristic of PGE2 signaling in immune cells, may provide attractive new avenues for cancer therapy.