肝癌细胞对成熟树突状细胞生物物理学特性的影响

The effect of hepatocellular carcinoma cells on the biophysical characteristics of mature dendritic cells

目的:研究肝癌细胞微环境成熟树突状细胞(Mature dendritic cells,mDCs)的生物物理学特性的影响,从交叉学科的角度来探索肿瘤细胞的免疫逃逸机制。方法:用免疫磁珠从人外周血分离CD14+单核细胞,加入rhGM-CSF和rhIL-4将单核细胞诱导分化为imDCs,利用TNF-α将未成熟树突状细胞(Immature dendritic cells,imDCs)诱导为mDCs,mDCs与HCCs在Transwell中共培养48h,分别利用微吸管法、荧光偏振法和Transwell法研究细胞粘弹性、膜流动性和迁移能力。结果:与肝癌细胞(Hepa tocellular carcinoma cells,HCCs)共培养后,mDCs的粘弹性和膜流动性显著下降,细胞的迁移能力受到显著的损伤。结论:HCCs可能能够损伤mDCs的生物物理学特性来影响其迁移能力,这可能是肿瘤逃脱机体免疫监视的方式之一,这对进一步深入理解肿瘤的免疫逃逸机制具有重要意义。

Objective：To study the influence of hepatocellular carcinoma cells microenvironment on the biophysical characteristics of mature dendritic cells（mDCs）and explore the immune escape mechanism of tumor cell from interdiscipline viewpoint.Methods：The monocytes were then cultured in RPMI1640/10% FBS supplemented with 100 ng/ml rhGM-CSF and 100 ng/ml rhIL-4 for 7 days to develop into immature DCs（imDCs）.mDCs was induced by addition of 20 ng/ml rhTNF-α to imDCs for another 3 days of culture.Acquired mDCs were co-cultured with human HCCs for 48 hours in Transwell.The treated cells were investigated the viscoelastic property,membrane fluidity and transendothelial migration by micropipette,fluorescence polarization and Transwell,respectively,untreated cells as control.Results：Compared with untreated DCs,the DCs co-cultured with HCC appeared decreased viscoelastic property,membrane fluidity and impaired transendothelial migration.Conclusion：HCCs can impaire the biophysical characteristics of mDCs leading to their deteriorated transendothelial migration.This might be one aspect of escape from immune surveillance of tumor.It is significant for further understanding the immune escape mechanism of tumor.