Blocking programmed death-ligand 1 attenuates maturation inhibition of dendritic cells by co-cultured breast cancer cells
YU Xiaoran
WEN Qiaosheng
XIAO Yi
TANG Rui
LI Fuxi
SHAO Wenfeng
YU Yanlin
XIONG Jingbo
Abstract：Objective To study if programmed death-ligand 1 (PL-L1) expression in breast cancer cell activates PD-L1/PD-1 pathway in dendritic cells to inhibit dendritic cell maturation.Methods Human monocytes were induced to differentiate into immature dendritic cells using GM-CSF and IL-4,and further to mature dendritic cells using TNF-α.PD-L1-expressing breast cancer cell line MDA-MB-231 was co-cultured in contact with the dendritic cells to observe the effects of the breast cancer cells on the maturation of the dendritic cells. A PD-L1 blocking antibody was applied to the co-culture, and the changes in the inhibitory effect of the MDA-MB-231 cells on dendritic cell maturation was observed. TNF-α-induced dendritic cells were treated with a recombinant human PD-L1 protein to study the effect of PD-L1/PD-1 pathway activation on the maturation of dendritic cells.The expression of PD-L1 in MDA-MB-231 cells and the dendritic cell maturation marker HLA-DR and CD83 were analyzed using flow cytometry. Results MDA-MB-231 cell line showed PD-L1 positivity on the cell membrane cells at a rate as high as(99.7±0.15)%.In mature dendritic cells,the positivity rates for HLA-DR and CD83 were(88.8±6.96)% and(18.36± 3.07)%, respectively, but in the co-culture system, the positivity rates of the dendritic cells were significantly decreased to (42.76±10.52)%(P<0.01)and(9.93±2.74)%(P<0.05),respectively,indicating that MDA-MB-231 cells inhibited the maturation of dendritic cells. Following treatment with a PD-L1 antibody isotype control, the percentages of HLA-DR- and CD83-positive cells in the co-culture were(45.17±10.19)% and(10.15±2.54)%,which were significantly increased to(63.46±1.72)% and(16.46± 2.58)% after treatment with PD-L1 antibody,respectively(both P<0.05).Compared with the mature dendritic cell controls,the cells treated with the recombinant human PD-L1 protein exhibited significantly lowered percentages of HLA-DR-positive [from(84.23±4.18)% to(2.56±2.39)%,P<0.05]and CD83-positive cells[(87.26±1.54)% to(60.67±1.63)%,P<0.05].Conclusion The effect of PD-L1 antibody therapy on triple negative breast cancer can be partially mediated by blocking PD-L1 expression on breast cancer cell membrane,which attenuates the inhibition of dendritic cell maturation in the cancer microenvironment.
Keywords：breast cancerprogrammed death-ligand 1programmed from cell death protein 1dendritic cell maturationcancer therapycancer microenvironment
Publication Date：2018-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 561-566 )