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Biomarkers in Adult-Type Diffuse Gliomas: Elevated Levels of Circulating Vesicular Heat Shock Protein 70 Serve as a Biomarker in Grade 4 Glioblastoma and Increase NK Cell Frequencies in Grade 3 Glioma

Affiliation
Central Institute for Translational Cancer Research Technische Universität München (TranslaTUM), Klinikum rechts der Isar, TUM School of Medicine and Health, 81675 Munich, Germany;(P.L.);(D.T.);(A.B.D.);(V.M.);(H.Z.);
Lennartz, Philipp;
Affiliation
Central Institute for Translational Cancer Research Technische Universität München (TranslaTUM), Klinikum rechts der Isar, TUM School of Medicine and Health, 81675 Munich, Germany;(P.L.);(D.T.);(A.B.D.);(V.M.);(H.Z.);
Thölke, Dennis;
Affiliation
Central Institute for Translational Cancer Research Technische Universität München (TranslaTUM), Klinikum rechts der Isar, TUM School of Medicine and Health, 81675 Munich, Germany;(P.L.);(D.T.);(A.B.D.);(V.M.);(H.Z.);
Bashiri Dezfouli, Ali;
Affiliation
Central Institute for Translational Cancer Research Technische Universität München (TranslaTUM), Klinikum rechts der Isar, TUM School of Medicine and Health, 81675 Munich, Germany;(P.L.);(D.T.);(A.B.D.);(V.M.);(H.Z.);
Pilz, Mathias;
ORCID
0000-0001-8442-6380
Affiliation
Department of Thoracic Surgery, München Klinik Bogenhausen, Lehrkrankenhaus der TUM, 81925 Munich, Germany;
Lobinger, Dominik;
ORCID
0009-0000-0314-2133
Affiliation
Central Institute for Translational Cancer Research Technische Universität München (TranslaTUM), Klinikum rechts der Isar, TUM School of Medicine and Health, 81675 Munich, Germany;(P.L.);(D.T.);(A.B.D.);(V.M.);(H.Z.);
Messner, Verena;
Affiliation
Central Institute for Translational Cancer Research Technische Universität München (TranslaTUM), Klinikum rechts der Isar, TUM School of Medicine and Health, 81675 Munich, Germany;(P.L.);(D.T.);(A.B.D.);(V.M.);(H.Z.);
Zanth, Hannah;
Affiliation
Central Institute for Translational Cancer Research Technische Universität München (TranslaTUM), Klinikum rechts der Isar, TUM School of Medicine and Health, 81675 Munich, Germany;(P.L.);(D.T.);(A.B.D.);(V.M.);(H.Z.);
Ainslie, Karen;
ORCID
0000-0001-5202-8505
Affiliation
Central Institute for Translational Cancer Research Technische Universität München (TranslaTUM), Klinikum rechts der Isar, TUM School of Medicine and Health, 81675 Munich, Germany;(P.L.);(D.T.);(A.B.D.);(V.M.);(H.Z.);
Kafshgari, Morteza Hasanzadeh;
Affiliation
Department of Anaesthesiology and Intensive Care Medicine, Klinikum rechts der Isar, TUM School of Medicine and Health, 81675 Munich, Germany(M.S.)
Rammes, Gerhard;
Affiliation
Department of Anaesthesiology and Intensive Care Medicine, Klinikum rechts der Isar, TUM School of Medicine and Health, 81675 Munich, Germany(M.S.)
Ballmann, Markus;
ORCID
0000-0001-7054-9566
Affiliation
Department of Anaesthesiology and Intensive Care Medicine, Klinikum rechts der Isar, TUM School of Medicine and Health, 81675 Munich, Germany(M.S.)
Schlegel, Martin;
Affiliation
John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK;(G.A.F.);(A.G.P.)
Foulds, Gemma Ann;
ORCID
0000-0001-9593-6431
Affiliation
John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK;(G.A.F.);(A.G.P.)
Pockley, Alan Graham;
Affiliation
Department of Neurology, Klinikum rechts der Isar, TUM School of Medicine and Health, 81675 Munich, Germany;
Schmidt-Graf, Friederike;
ORCID
0000-0002-2616-3137
Affiliation
Central Institute for Translational Cancer Research Technische Universität München (TranslaTUM), Klinikum rechts der Isar, TUM School of Medicine and Health, 81675 Munich, Germany;(P.L.);(D.T.);(A.B.D.);(V.M.);(H.Z.);
Multhoff, Gabriele

The presence of circulating Hsp70 levels and their influence on the immunophenotype of circulating lymphocyte subsets were examined as diagnostic/prognostic biomarkers for the overall survival (OS) in patients with IDH-mutant WHO grade 3 oligodendroglioma, astrocytoma, and IDH-wildtype grade 4 glioblastoma (GBM). Vesicular and free Hsp70 in the plasma/serum was measured using the Hsp70-exo and R&D Systems DuoSet ® Hsp70 ELISAs. The immunophenotype and membrane Hsp70 status was determined by multiparameter flow cytometry on peripheral blood lymphocytes and single-cell suspensions of tumor specimens and cultured cells. Compared to healthy controls, circulating vesicular Hsp70 levels were significantly increased in patients with GBM, concomitant with a significant decrease in the proportion of CD3+/CD4+ helper T cells, whereas the frequency of NK cells was most prominently increased in patients with grade 3 gliomas. Elevated circulating Hsp70 levels and a higher prevalence of activated CD3−/CD56+/CD94+/CD69+ NK cells were associated with an improved OS in grade 3 gliomas, whereas high Hsp70 levels and low CD3+/CD4+ frequencies were associated with an adverse OS in GBM. It is assumed that a reduced membrane Hsp70 density on grade 4 versus grade 3 primary glioma cells and reduced CD3+/CD4+ T cell counts in GBM might drive an immunosuppressive tumor microenvironment.

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Editor:
Sa, Jason K.; Kanakis, Dimitrios
Published in:
Biomedicines  
Vol. 11, No. 12 (07.12.2023)
Volume:
11
No.:
12
Date Issued:
07.12.2023
DOI:
10.3390/biomedicines11123235
Language:
English
Type of Resource:
Text
Keywords:
  1. biomarkers
    Typ
    Schlagwort
  1. liquid biopsy
    Typ
    Schlagwort
  1. extracellular free and vesicular Hsp70
    Typ
    Schlagwort
  1. plasma membrane bound Hsp70
    Typ
    Schlagwort
  1. glioblastoma
    Typ
    Schlagwort
  1. oligodendroglioma
    Typ
    Schlagwort
  1. astrocytoma
    Typ
    Schlagwort
  1. isocitrate dehydrogenase 1/2
    Typ
    Schlagwort
  1. NK cells
    Typ
    Schlagwort
  1. immunophenotyping
    Typ
    Schlagwort
DDC:
610 Medizin und Gesundheit

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