Advances in the role of cyclooxygenase 2 inhibitors in hepatocellular carcinoma via regulatory T lymphocytes
Liver cancer is the third leading cause of cancer-related deaths globally,with hepatocellular carci-noma(HCC)being the predominant type.By the time most patients are diagnosed with HCC,they have often lost the opportunity for surgical resection or ablation.The immune response within the liver plays a crucial role in the occur-rence and progression of HCC.In recent years,as our understanding of the hepatic microenvironment has deepened,the treatment strategies for HCC have shifted from direct targeting of cancer cells to modulating the liver's immune mi-croenvironment.Both innate and adaptive immunity play significant roles in this context,and their imbalance may be a key factor in the progression of HCC.Notably,regulatory T cells(Tregs)are essential for immune regulation;reducing the frequency of Tregs can effectively activate both innate and adaptive immune responses against HCC.Cyclooxygen-ase-2(COX-2)inhibitors may play an important role in decreasing Treg frequencies by enhancing the Enclysis pathway(a liver-specific mechanism for phagocytosing Tregs)and reducing the expression of prostaglandins E and D.This pa-per hypothesizes that COX-2 inhibitors can lower Treg frequencies and enhance both innate and adaptive immunity to treat HCC.It will elaborate on the relevant signaling pathways and mechanisms involved,providing strategies for the combined treatment of advanced hepatocellular carcinoma.
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