目的：探究中链脂肪酸癸酸对CD8+ T细胞活化的影响，及其对CD8+ T细胞介导的抗肿瘤免疫反应的作用和机制。方法：建立C57BL/6小鼠黑色素瘤B16F10 皮下荷瘤模型，随机分为癸酸组（10 mg/kg 癸酸灌胃）和对照组（等量溶剂灌胃），观察癸酸对小鼠肿瘤生长以及生存率的影响，采用流式细胞术检测肿瘤微环境中浸润CD8+ T细胞的活化水平。建立B16F10-OVA和OT-I T细胞共培养体系，采用流式细胞术检测癸酸对CD8+ T细胞的肿瘤细胞杀伤能力的影响。采用α-CD8抗体清除B16F10 荷瘤小鼠体内CD8+ T细胞，观察对小鼠肿瘤体积的影响。小鼠原代CD8+ T细胞经癸酸处理后，采用WB、ELISA及qPCR、流式细胞术检测T细胞受体（TCR）活化、效应细胞因子产生以及增殖和代谢水平。在B16F10荷瘤小鼠模型中，观察α-PD-1抗体联合癸酸给药对小鼠肿瘤生长以及生存率的影响。结果：在小鼠黑色素瘤荷瘤模型中，与对照组相比，癸酸组小鼠移植瘤体积显著降低且生存率显著提高（均P<0.05），肿瘤浸润CD8+ T细胞IFN-γ和TNF-α的表达水平显著升高（P<0.01）。经癸酸处理的OT-I T细胞对B16F10-OVA细胞的杀伤水平显著升高（P<0.01）。在荷瘤小鼠模型中用α-CD8 抗体清除CD8+ T 细胞后，癸酸对移植瘤的抑制作用显著降低（P<0.000 1）。小鼠原代CD8+ T细胞经癸酸处理后，TCR活化水平显著升高、细胞因子IL-2和IFN-γ的产生增多、线粒体代谢水平显著上调（均P<0.05）。在黑色素瘤荷瘤小鼠模型中，癸酸与α-PD-1抗体联用，能够显著抑制小鼠移植瘤生长并提高其生存率（均P<0.05）。结论：癸酸能够促进CD8+ T细胞活化、增强其抗肿瘤免疫反应能力。

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.

国家自然科学基金（No. 82371755）；上海交通大学“交大之星”计划医工交叉研究基金（No. YG2023QNA40）