| Autor: |
Xiao-Ran, Yu, Qiao-Sheng, Wen, Yi, Xiao, Rui, Tang, Fu-Xi, Li, Wen-Feng, Shao, Yan-Lin, Yu, Jing-Bo, Xiong |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
Nan fang yi ke da xue xue bao = Journal of Southern Medical University. 38(5) |
| ISSN: |
1673-4254 |
| Popis: |
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]. CONCLUSIONS: 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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