期刊
STEM CELL RESEARCH & THERAPY
卷 13, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13287-022-02968-z
关键词
Glioma-associated mesenchymal stem cells; PD-L1; Glioblastoma; Oncolytic virus; Angiogenesis
资金
- Beijing Natural Science Foundation Program and Scientific Research Key Program of the Beijing Municipal Commission of Education [KZ202010025034]
- Capital's Funds for Health Improvement and Research (CFH) [2020-1-1071]
- National Natural Science Foundation of China [81972344, 81672478]
- Natural Science Foundation of Beijing Municipality [7202020]
- Beijing Laboratory of Biomedical Materials Foundation
The study found that glioma-associated mesenchymal stem cells (GA-MSCs) have the potential to induce upregulation of programmed death ligand 1 (PD-L1) in glioma cells and are involved in vascular mimicry. Importantly, oncolytic Ad5-Ki67/IL-15 reduced PD-L1 expression in glioma cells and neovascularization by targeting GA-MSCs. Furthermore, despite the presence of GA-MSCs, the virus showed potent antitumor efficacy in vitro and in vivo.
Background Glioblastoma (GBM) is a highly immunosuppressive and vascular malignant brain tumor. Current therapeutic strategies targeting tumor cells have limited efficacy because of the immunosuppressive microenvironment and vascularization. Glioma-associated mesenchymal stem cells (GA-MSCs) have been identified as important stromal components of the tumor microenvironment, owing to their contribution to tumor angiogenesis and their potential to drive glioma stem cells. However, there are no reports on the effect of oncolytic Ad5-Ki67/IL-15 on programmed death ligand 1 (PD-L1) expression and angiogenesis induced by GA-MSCs. Methods Flow cytometry was respectively performed to detect the PD-L1 of glioma cells and programmed death protein 1 (PD-1), CD3, CD4 and CD8 in lymphocytes, as well as distribution of the cell cycle. CCK-8 assay investigated the proliferation of glioma cells and GA-MSCs in vitro. Tumor-bearing nude mice were established with U87-Luc cells and treated with the viruses, and further the IVIS spectrum was utilized to obtain luciferase images. Finally, the expression of PD-L1 in tumor tissues was also investigated using western blotting. Results We found that GA-MSCs had potential to induce PD-L1 upregulation and involved in vascular mimicry in vitro. Importantly, Ad5-Ki67/IL-15 reduced PD-L1 expression of glioma cells and neovascularization by targeting GA-MSCs. Furthermore, despite the presence of GA-MSCs, the virus has the ability to generate potent antitumor efficacy in vitro and vivo. Conclusions These findings suggest the use of oncolytic Ad5-Ki67/IL-15 targeting GA-MSCs to treat GBM, indicating potential clinical applications.
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