Pla2g7, encoding platelet activating factor acetyl hydrolase, is a pivotal enzyme in phospholipid metabolism [1,3,5,6]. It is involved in multiple biological processes, and its dysregulation is associated with various diseases [1,2,3,4,5,6,7]. Gene knockout (KO) and conditional knockout (CKO) mouse models are valuable for studying its functions.

In hepatocellular carcinoma (HCC), macrophage-specific Pla2g7 is correlated with poorer prognosis and immunotherapy resistance. Inhibiting Pla2g7 by darapladib in mouse models improves the efficacy of anti-programmed cell death protein 1 antibodies, reversing the immunosuppressive function of intratumoral macrophages [1].

In pulmonary fibrosis, Pla2g7high macrophages promote fibroblast-to-myofibroblast transition, and darapladib-mediated inhibition of Pla2g7 ameliorates pulmonary fibrosis in bleomycin-induced mice [2].

Deletion of Pla2g7 in mice shows decreased thymic lipoatrophy, protection against age-related inflammation, and improved metabolic health, suggesting its role in the immunometabolic effects of caloric restriction [3].

In bladder cancer, knockdown of Pla2g7 in syngeneic mouse models inhibits PD-L1 expression, promotes CD8+ T-cell infiltration, and suppresses tumor growth. Additionally, suppression of Pla2g7 and anti-CTLA4 therapy have synergistic effects on tumor burden and mouse survival [4].

In summary, Pla2g7 plays diverse roles in multiple biological processes and diseases. Model-based research, especially KO/CKO mouse models, has revealed its significance in immunotherapy resistance, fibrosis, immunometabolism, and tumor immune evasion. Understanding Pla2g7 provides potential therapeutic strategies for diseases such as HCC, pulmonary fibrosis, and bladder cancer.