Lipid accumulation and dendritic cell dysfunction in cancer
Lipid accumulation and dendritic cell dysfunction in cancer
复制标题
癌症中的脂质积累和树突状细胞功能障碍
DOI：
10.1038/nm.2172
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发表时间：
2010-08-01
期刊：
影响因子：
82.9
通讯作者：
Gabrilovich, Dmitry I.
中科院分区：
文献类型：
--
作者：
Herber, Donna L.;Cao, Wei;Gabrilovich, Dmitry I.
树突状细胞（Dendritic cells，DCs）是一类专职的抗原提呈细胞，负责免疫应答的启动和维持。在这里，我们报告说，与来自无肿瘤小鼠和健康个体的DC相比，荷瘤小鼠和癌症患者中很大一部分DC具有大量的甘油三酯。在我们的研究中，DC中的脂质积聚是由清道夫受体A的上调引起的细胞外脂质摄取增加引起的。高脂质含量的DC不能有效地刺激同种异体T细胞或呈递肿瘤相关抗原。高脂和正常脂水平的DC在主要组织相容性复合物和共刺激分子的表达上没有差异。然而，脂质负载的DC处理抗原的能力降低。用乙酰辅酶A羧化酶抑制剂使树突状细胞中脂质丰度的药理学正常化恢复了树突状细胞的功能活性，并大大增强了癌症疫苗的效果。这些发现表明，癌症中的免疫反应可以通过操纵DC中的脂质水平来改善。
Dendritic cells (DCs), a type of professional antigen-presenting cells, are responsible for initiation and maintenance of immune responses. Here we report that a substantial proportion of DCs in tumor-bearing mice and people with cancer have high amounts of triglycerides as compared with DCs from tumor-free mice and healthy individuals. In our studies, lipid accumulation in DCs was caused by increased uptake of extracellular lipids due to upregulation of scavenger receptor A. DCs with high lipid content were not able to effectively stimulate allogeneic T cells or present tumor-associated antigens. DCs with high and normal lipid levels did not differ in expression of major histocompatibility complex and co-stimulatory molecules. However, lipid-laden DCs had a reduced capacity to process antigens. Pharmacological normalization of lipid abundance in DCs with an inhibitor of acetyl-CoA carboxylase restored the functional activity of DCs and substantially enhanced the effects of cancer vaccines. These findings suggest that immune responses in cancer can be improved by manipulating the lipid levels in DCs.