Experimental study of Maresin-1 regulating PD-1-induced cytotoxic T cells in the treatment of hepatocellular carcinoma

YING Lichao; CHI Jinzheng; ZHANG Yu

doi:10.3969/j.issn.1009-0460.2025.03.001

Abstract：Objective To investigate the role of Maresin-1 in hepatocellular carcinoma and its effect on cytotoxic T cells.Methods Sixty 5-week-old BALB/c mice were randomly divided into control group,model group,low-dose group,and high-dose group.Mouse hepatocellular carcinoma models were constructed by in situ inoculation of H22 cells.Low-dose and high-dose groups of mice were intraperitoneally injected with 25 ng/kg and 100 ng/kg Maresin-1 on the basis of in situ inoculation.After 2 weeks,the volume of cancer was evaluated,and serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(STB)levels were measured.Flow cytometry was used to detected the expression of cytotoxic T lymphocytes in mouse hepatocellular carcinoma and the expression of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and lymphatic toxins-α(LT-A)were detected.Western blot was used to detect the expression of PD-1 and PD-L1 in hepatocellular carcinoma tissue.Results Compared with the control group,the volume of liver cancer tissues,Ki-67 expression,and the contents of serum ALT,and STB in the model group were significantly increased(P<0.05).Compared with the control group,the levels of cytotoxic T lymphocytes,TNF-α,IFN-γ,and LT-A in the liver cancer tissues of the model group were significantly decreased,while the expressions of PD-1 and PD-L1were significantly increased(P<0.05).Compared with the model group,the volume of liver cancer tissues,Ki67 expression,and the contents of serum ALT,AST,and STB in the low-dose groups were significantly decreased(P<0.05).Compared with the model group,the levels of cytotoxic T lymphocytes,TNF-α,IFN-γ,and LT-A in the low-dose groups were significantly increased,while the expressions of PD-1 and PD-L1 were significantly decreased(P<0.05).Compared with the model group,the volume of liver cancer tissue,Ki-67 expression,and the levels of serum ALT,AST,and STB in the high-dose group were significantly decreased(P<0.05).Compared with the model group,the levels of cytotoxic T lymphocytes,TNF-α,IFN-γ,and LT-A in the high-dose group were significantly increased,while the expressions of PD-1 and PD-L1 were significantly decreased(P<0.05).Conclusion Maresin-1 promotes the effect of cytotoxic T lymphocytes on hepatocellular carcinoma by inhibiting the PD-1/PD-L1 pathway.