Back
Full-text
Journal article

Exosomes isolated from plasma of glioma patients enrolled in a vaccination trial reflect antitumor immune activity and might predict survival.

  • Muller L University of Pittsburgh Cancer Institute ; Pittsburgh, PA, USA ; Department of Otolaryngology and Head & Neck Surgery; University Hospital Basel ; Basel, Switzerland.
  • Muller-Haegele S University of Pittsburgh Cancer Institute ; Pittsburgh, PA, USA.
  • Mitsuhashi M Hitachi Chemical Research Center, Inc. ; Irvine, CA, USA.
  • Gooding W University of Pittsburgh Cancer Institute ; Pittsburgh, PA, USA.
  • Okada H University of Pittsburgh Cancer Institute ; Pittsburgh, PA, USA ; Departments of Neurological Surgery; Surgery and Immunology; University of Pittsburgh School of Medicine ; Pittsburgh, PA, USA.
  • Whiteside TL University of Pittsburgh Cancer Institute ; Pittsburgh, PA, USA ; Departments of Pathology; Immunology and Otolaryngology; University of Pittsburgh School of Medicine ; Pittsburgh, PA, USA.
Show more…
  • 2015-07-09
Published in:
  • Oncoimmunology. - 2015
AA, anaplastic astrocytoma
AO, anaplastic oligodendroglioma
ATP, adenosine triphosphates
EV, extracellular vesicles
GAA, glioma associated antigens
GBM, glioblastoma multiforme
MRI, magnetic resonance imaging
NC, normal controls
OS, overall survival
PD-1, programmed death-1
PD-L1, programmed death ligand 1
TEM, transmission electron microscopy
TEX, tumor-derived exosomes
TTP, time to progression
glioma
mRNA
plasma-derived exosomes
survival
vaccination
English Exosomes in plasma of glioma patients hold promise as biomarkers of prognosis. We aimed to determine whether changes in total exosomal protein and mRNA expression levels could serve as surrogate markers of immunological and clinical responses in glioma patients receiving antitumor vaccines. Exosomes were isolated from pre/post-vaccine plasma specimens in 20/22 patients enrolled in a phase I/II trial with the antitumor vaccine. Exosomal protein content was analyzed and mRNA expression levels for 24 genes were simultaneously assessed by qRT-PCR. Pre- to post-vaccination changes in exosomal protein and ΔCt values were correlated with immunological and clinical responses and survival using Spearman rank statistics and hazard ratios (HR). Exosomal protein levels positively correlated (p < 0.0043) with the WHO tumor grade at diagnosis. Protein levels were lower in post- vs. pre-vaccination exosome fractions. Post-therapy increases in tumor size were associated with elevations in exosome proteins in glioblastoma but not always in anaplastic astrocytoma (AA). Only exosomal ΔCt values for IL-8, TIMP-1, TGF-β and ZAP70 were significant (p < 0.04 to p < 0.001). The ΔCt for IL-8 and TGF-β mRNA positively correlated with post-vaccine immunologic responses to glioma antigens, while ΔCt for TIMP-1 mRNA was negatively correlated to ΔCt for IL-8 and TGF-β. Only ΔCt for IL-8 weakly correlated with OS and time to progression (TTP). In post-vaccine exosomes of the longest surviving patient with AA, mRNA for PD-1 was persistently elevated. Protein and mRNA expression levels for immune-related genes in plasma exosomes were useful in evaluating glioma patients' response to vaccination therapy.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/123725
Statistics
Document views: 34 File downloads:
  • Full-text: 0