MicroRNA-200a induces immunosuppression by promoting PTEN-mediated PD-L1 upregulation in osteosarcoma.

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ID: 86818
2020
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Abstract
In this study, we identified microRNAs that regulate the expression of programmed death-ligand 1(PD-L1) in osteosarcoma and investigated their role in PD-L1-targeted immunotherapy. MicroRNA sequencing analysis showed that the expression of PD-L1 is regulated by microRNA-200a in U2OS, 143B, and K7 osteosarcoma cells. MicroRNA-200a overexpression induced the upregulation of PD-L1 in the osteosarcoma cells. CD8 T cells co-cultured with microRNA-200a-overexpressing osteosarcoma cells showed reduced survival, proliferation, and secretion of granzyme B and perforin. The same phenomenon was also observed in the K7-derived syngeneic mouse model, as microRNA-200a promoted tumor growth by increasing the percentage of Foxp3 regulatory T lymphocytes while reducing the proportions of CD4, CD8, and IFN-γ cytotoxic T lymphocytes. But microRNA-200a overexpression group was also more responsive to PD-L1-targeted immunotherapy than the controls. In addition, the tumor tissues from 32 osteosarcoma patients showed that high expression of microRNA-200a and PD-L1 was associated with poor tumor necrosis rate after chemotherapy. Moreover, we confirmed that tensin homolog deleted on chromosome ten (PTEN) could act as the target gene for microRNA-200a during the upregulation of PD-L1. Thus, our findings provide important and novel insight into a regulatory axis involving microRNA-200a/PTEN/ PD-L1 axis, which determines osteosarcoma growth and the efficacy of PD-L1-targeted immunotherapy.
Reference Key
liu2020microrna200aaging Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Liu, Zhuochao;Wen, Junxiang;Wu, Chuanlong;Hu, Chuanzhen;Wang, Jun;Bao, Qiyuan;Wang, Hongyi;Wang, Jizhuang;Zhou, Qi;Wei, Li;Shen, Yuhui;Zhang, Weibin;
Journal Aging
Year 2020
DOI
10.18632/aging.102679
URL
Keywords
pd-l1 immunosuppression pten cd8+ t cells microrna-200a

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