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目的探讨肿瘤微环境中的乳酸对树突状细胞(dendritic cells,DC)活化和功能的影响。方法取C57BL/6小鼠骨髓细胞诱导其分化为DC,并加入脂多糖(lipopolysaccharides,LPS)促进其活化;随后采用肿瘤培养上清或乳酸作用于活化的DC,通过流式细胞术、ELISA、T细胞增殖实验、Western blot等方法检测DC细胞的活化程度,并对乳酸影响DC活化的信号通路进行分析。结果乏氧状态的肿瘤细胞释放更多的乳酸,乳酸可以抑制DC细胞共刺激因子CD80、CD86和MHCⅡ的表达,并下调TNF-α和IL-12的表达,从而抑制DC对T细胞活化增殖的促进作用;乳酸通过降低DC的NF-κB和p38MAPK信号通路的活化影响DC活化。结论肿瘤组织乏氧状态释放大量的乳酸,乳酸通过抑制DC细胞的活化进而影响抗肿瘤免疫反应的激活。
Objective To investigate the effect of lactic acid on the activation and function of dendritic cells (DCs) in tumor microenvironment. Methods Bone marrow cells of C57BL / 6 mice were induced to differentiate into DCs and activated with lipopolysaccharides (LPS). The cultured DCs or lactic acid were used to activate DCs. Flow cytometry, ELISA, T cell proliferation assay, Western blot and other methods to detect the activation of DC cells, and lactic acid activation of DC signaling pathway analysis. Results Lack of lactic acid was released from tumor cells in hypoxic condition. Lactic acid could inhibit the expression of CD80, CD86 and MHC Ⅱ of DCs and down-regulate the expression of TNF-α and IL-12, thereby inhibiting the proliferation of T cells Lactic acid affects DC activation by decreasing the activation of NF-κB and p38MAPK signaling in DCs. Conclusion Lack of lactic acid is released from hypoxia in tumor tissue. Lactic acid affects the activation of anti-tumor immune response by inhibiting the activation of DC cells.