Journal
ONCOTARGET
Volume 8, Issue 16, Pages 26256-26268Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15445
Keywords
EGFRvIII; dendritic cell vaccine; miR-326; hedgehog signalling pathway; TGF-beta 1
Categories
Funding
- Research Special Fund for Public Welfare Industry of Heath [201402008]
- National Key Research and Development Plan [2016YFC0902500]
- China National Natural Scientific Fund [81372700, 81402053, 81572701, 81472347]
- China Postdoctoral Science Foundation [2013M531121]
- Shanghai Postdoctoral Science Foundation [13R21411300]
- China Postdoctoral Science special Foundation [2014T70390]
- Special Fund Project of Translational Medicine in the Chinese-Russian Medical Research Centre [CR201417]
- Research Project of Chinese Society of Neuro-oncology, CACA [CSNO-2014-MSD08]
- Heilongjiang Province Postdoctoral Science Foundation [LBH-Z14220]
- Heilongjiang Province Natural Scientific Fund [H201417]
- Research Project of Heilongjiang Provincial Health Department [2013048]
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The mutant Type III variant of epidermal growth factor receptor (EGFRvIII) is present in approximately one-third of glioblastoma (GBM) patients. It is never found in normal tissues; therefore, it represents a candidate target for GBM immunotherapy. PEPvIII, a peptide sequence from EGFRvIII, was designed to represent a target of glioma and is presented by MHC I/II complexes. Dendritic cells (DCs) have great potential to sensitize CD4(+) T and CD8(+) T cells to precisely target and eradicate GBM. Here, we show that PEPvIII could be loaded by DCs and presented to T lymphocytes, especially PEPvIII-specific CTLs, to precisely kill U87-EGFRvIII cells. In addition to inhibiting proliferation and inducing the apoptosis of U87-EGFRvIII cells, miR-326 also reduced the expression of TGF-beta 1 in the tumour environment, resulting in improved efficacy of T cell activation and killing via suppressing the SMO/Gli2 axis, which at least partially reversed the immunosuppressive environment. Furthermore, combining the EGFRvIII-DC vaccine with miR-326 was more effective in killing U87-EGFRvIII cells compared with the administration of either one alone. This finding suggested that a DC-based vaccine combined with miR-326 may induce more powerful antitumour immunity against GBM cells that express a relevant antigen, which provides a promising approach for GBM immunotherapy.
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