中国肿瘤生物治疗杂志2024，Vol.31Issue(5)：437-444,8.DOI:10.3872/j.issn.1007-385x.2024.05.002
癸酸能够活化CD8+T细胞并提高其抗肿瘤免疫反应能力
Decanoic acid activates CD8+T cells and enhances their anti-tumor immune responses
摘要
Abstract
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.关键词
抗肿瘤免疫/癸酸/CD8+T细胞/程序性死亡蛋白-1Key words
anti-tumor immunity/decanoic acid/CD8+T cell/programmed death protein-1(PD-1)分类
医药卫生引用本文复制引用
张翀,金海振,周纯,胡惠惠,王娟,王秦兰..癸酸能够活化CD8+T细胞并提高其抗肿瘤免疫反应能力[J].中国肿瘤生物治疗杂志,2024,31(5):437-444,8.基金项目
国家自然科学基金(No.82371755) （No.82371755）
上海交通大学"交大之星"计划医工交叉研究基金(No.YG2023QNA40) （No.YG2023QNA40）
