PMID- 28412740 OWN - NLM STAT- MEDLINE DCOM- 20180305 LR - 20181202 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 16 DP - 2017 Apr 18 TI - Combination epidermal growth factor receptor variant III peptide-pulsed dendritic cell vaccine with miR-326 results in enhanced killing on EGFRvIII-positive cells. PG - 26256-26268 LID - 10.18632/oncotarget.15445 [doi] AB - 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-beta1 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 anti-tumour immunity against GBM cells that express a relevant antigen, which provides a promising approach for GBM immunotherapy. FAU - Li, Jianlong AU - Li J AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. AD - Neuroscience Institute, Heilongjiang Academy of Medical Sciences, Harbin 150086, China. AD - Chinese Glioma Cooperative Group (CGCG), Beijing 100050, China. FAU - Wang, Feng AU - Wang F AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. AD - Chinese Glioma Cooperative Group (CGCG), Beijing 100050, China. FAU - Wang, Guangzhi AU - Wang G AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Sun, Ying AU - Sun Y AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. AD - Chinese Glioma Cooperative Group (CGCG), Beijing 100050, China. FAU - Cai, Jinquan AU - Cai J AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. AD - Neuroscience Institute, Heilongjiang Academy of Medical Sciences, Harbin 150086, China. AD - Chinese Glioma Cooperative Group (CGCG), Beijing 100050, China. FAU - Liu, Xing AU - Liu X AD - Chinese Glioma Cooperative Group (CGCG), Beijing 100050, China. AD - Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. FAU - Zhang, Junhe AU - Zhang J AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. AD - Chinese Glioma Cooperative Group (CGCG), Beijing 100050, China. FAU - Lu, Xiaoyan AU - Lu X AD - Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Li, Yongli AU - Li Y AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. AD - Chinese Glioma Cooperative Group (CGCG), Beijing 100050, China. FAU - Chen, Meng AU - Chen M AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Chen, Lingchao AU - Chen L AD - Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China. AD - Chinese Glioma Cooperative Group (CGCG), Beijing 100050, China. FAU - Jiang, Chuanlu AU - Jiang C AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. AD - Neuroscience Institute, Heilongjiang Academy of Medical Sciences, Harbin 150086, China. AD - Chinese Glioma Cooperative Group (CGCG), Beijing 100050, China. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Cancer Vaccines) RN - 0 (GLI2 protein, human) RN - 0 (MIRN326 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Nuclear Proteins) RN - 0 (Peptides) RN - 0 (SMO protein, human) RN - 0 (Smoothened Receptor) RN - 0 (Transforming Growth Factor beta1) RN - 0 (Zinc Finger Protein Gli2) RN - 0 (epidermal growth factor receptor VIII) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Cancer Vaccines/*immunology MH - Cell Line, Tumor MH - Cytotoxicity, Immunologic MH - Dendritic Cells/*immunology/metabolism MH - ErbB Receptors/chemistry/*immunology MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Immunotherapy MH - Lymphocyte Activation MH - MicroRNAs/*genetics MH - Neoplasms/*genetics/*immunology/pathology/therapy MH - Nuclear Proteins/metabolism MH - Peptides/chemistry/*immunology MH - Signal Transduction MH - Smoothened Receptor/metabolism MH - T-Lymphocytes, Cytotoxic/immunology/metabolism MH - Transforming Growth Factor beta1/genetics/metabolism MH - Zinc Finger Protein Gli2/metabolism PMC - PMC5432254 OTO - NOTNLM OT - EGFRvIII OT - TGF-beta1 OT - dendritic cell vaccine OT - hedgehog signalling pathway OT - miR-326 COIS- CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest. EDAT- 2017/04/17 06:00 MHDA- 2018/03/06 06:00 PMCR- 2017/04/18 CRDT- 2017/04/17 06:00 PHST- 2016/10/04 00:00 [received] PHST- 2017/02/06 00:00 [accepted] PHST- 2017/04/17 06:00 [pubmed] PHST- 2018/03/06 06:00 [medline] PHST- 2017/04/17 06:00 [entrez] PHST- 2017/04/18 00:00 [pmc-release] AID - 15445 [pii] AID - 10.18632/oncotarget.15445 [doi] PST - ppublish SO - Oncotarget. 2017 Apr 18;8(16):26256-26268. doi: 10.18632/oncotarget.15445.