癸酸能够活化CD8+T细胞并提高其抗肿瘤免疫反应能力OA北大核心CSTPCD

Objective:To explore the effect of midchain fatty acid decanoic acid on CD8+T cell activation and its effect and mechanism in CD8+T cell-mediated anti-tumor immune response.Methods:Subcutaneous melanoma B16F10 cells tumor-bearing C57BL/6 mouse models were established and randomly divided into the decanoic acid group(10 mg/kg decanoic acid by gavage)and the control group(equal amount of solvent by gavage).The effect of decanoic acid on the growth of mouse tumors and their survival rate were measured.The activation of tumor-infiltrated CD8+T cells in the tumor microenvironment was detected by flow cytometry.The α-CD8 mAb was used to deplete CD8+T cells in B16F10 tumor-bearing mice,and the effect on the tumor volume was observed.Mouse primary CD8+T cells were treated with decanoic acid,and T cell receptor(TCR)activation,effector cytokine production as well as proliferation and metabolism levels were detected by WB,ELISA,qPCR,and flow cytometry.In B16F10 tumor-bearing mouse model,the effects of administration of α-PD-1 mAb combined with decanoic acid on the growth of mouse tumors and mouse survival rate were observed.Results:In the mouse melanoma model,compared with those in the control group the volume of mouse transplanted tumors significantly reduced and mouse survival rate significantly increased in the decanoic acid group.(both P<0.05).The expression levels of IFN-γ and TNF-α in tumor-infiltrating CD8+T cells were significantly higher in the decanoic acid group than that in the control group(P<0.01).The killing ability of OT-I T cells against B16F10-OVA cells was significantly elevated after treatment with decanoic acid(P<0.01).The suppressive effect of decanoic acid on transplanted tumors was significantly reduced after CD8+T cells were depleted with α-CD8 mAb in the melanoma mouse model(P<0.000 1).Mouse-derived primary CD8+T cells treated with decanoic acid showed significantly higher levels of TCR activation,increased production of cytokines IL-2 and IFN-γ,and significantly up-regulated the mitochondrial metabolic level(all P<0.05).In the melanoma mouse model,decanoic acid in combination with α-PD-1 mAb significantly inhibited tumor growth and increased the survival rate(both P<0.05).Conclusion:Decanoic acid can enhance the anti-tumor immune responses by promoting CD8+T cell activation.