Combined proteomics/miRNomics of dendritic cell immunotherapy-treated glioblastoma patients as a screening for survival-associated factors.

Autor:	Erhart F; 1Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.; 2Institute of Neurology, Medical University of Vienna, Vienna, Austria.; 3Department of Tumor Immunology, St. Anna Kinderkrebsforschung Children's Cancer Research Institute, Vienna, Austria., Hackl M; TAmiRNA GesmbH, Vienna, Austria., Hahne H; OmicScouts GmbH, Freising, Germany., Buchroithner J; 6University Clinic for Neurosurgery, Kepler University Hospital, Johannes Kepler University, Linz, Austria., Meng C; 7Chair of Proteomics and Bioanalytics, Technical University of Munich, Freising, Germany., Klingenbrunner S; Activartis Biotech GmbH, Vienna, Austria., Reitermaier R; Activartis Biotech GmbH, Vienna, Austria., Fischhuber K; Activartis Biotech GmbH, Vienna, Austria., Skalicky S; TAmiRNA GesmbH, Vienna, Austria., Berger W; 9Institute for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Spiegl-Kreinecker S; 6University Clinic for Neurosurgery, Kepler University Hospital, Johannes Kepler University, Linz, Austria., Lötsch D; 9Institute for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Ricken G; 2Institute of Neurology, Medical University of Vienna, Vienna, Austria., Kuster B; 7Chair of Proteomics and Bioanalytics, Technical University of Munich, Freising, Germany., Wöhrer A; 2Institute of Neurology, Medical University of Vienna, Vienna, Austria., Widhalm G; 1Department of Neurosurgery, Medical University of Vienna, Vienna, Austria., Hainfellner J; 2Institute of Neurology, Medical University of Vienna, Vienna, Austria., Felzmann T; Activartis Biotech GmbH, Vienna, Austria.; 10Research & Development, Central Blood Bank, Austrian Red Cross, Vienna, Austria., Dohnal AM; 3Department of Tumor Immunology, St. Anna Kinderkrebsforschung Children's Cancer Research Institute, Vienna, Austria., Marosi C; 11Clinical Division of Medical Oncology, Medical University of Vienna, Vienna, Austria., Visus C; Activartis Biotech GmbH, Vienna, Austria.
Jazyk:	angličtina
Zdroj:	NPJ vaccines [NPJ Vaccines] 2020 Jan 16; Vol. 5 (1), pp. 5. Date of Electronic Publication: 2020 Jan 16 (Print Publication: 2020).
DOI:	10.1038/s41541-019-0149-x
Abstrakt:	Glioblastoma is the most prevalent and aggressive brain cancer. With a median overall survival of ~15-20 months under standard therapy, novel treatment approaches are desperately needed. A recent phase II clinical trial with a personalized immunotherapy based on tumor lysate-charged dendritic cell (DC) vaccination, however, failed to prolong survival. Here, we investigated tumor tissue from trial patients to explore glioblastoma survival-related factors. We followed an innovative approach of combining mass spectrometry-based quantitative proteomics ( n  = 36) with microRNA sequencing plus RT-qPCR ( n  = 38). Protein quantification identified, e.g., huntingtin interacting protein 1 (HIP1), retinol-binding protein 1 (RBP1), ferritin heavy chain (FTH1) and focal adhesion kinase 2 (FAK2) as factor candidates correlated with a dismal prognosis. MicroRNA analysis identified miR-216b, miR-216a, miR-708 and let-7i as molecules potentially associated with favorable tissue characteristics as they were enriched in patients with a comparably longer survival. To illustrate the utility of integrated miRNomics and proteomics findings, focal adhesion was studied further as one example for a pathway of potential general interest. Taken together, we here mapped possible drivers of glioblastoma outcome under immunotherapy in one of the largest DC vaccination tissue analysis cohorts so far-demonstrating usefulness and feasibility of combined proteomics/miRNomics approaches. Future research should investigate agents that sensitize glioblastoma to (immuno)therapy-potentially building on insights generated here. Competing Interests: Competing interestsC.V., S.K., K.F. and R.R. were employees of Activartis Biotech GmbH at the time of this investigation. F.E. and A.M.D. were formerly (part‐time) employees of Activartis Biotech GmbH. The authors declare that the research was conducted in the absence of any other commercial, financial or personal relationships that could be construed as a potential competing interest. (© The Author(s) 2020.)
Databáze:	MEDLINE
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