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.

Lennartz, Philipp; Thölke, Dennis; Bashiri Dezfouli, Ali; Pilz, Mathias; Lobinger, Dominik; Messner, Verena; Zanth, Hannah; Ainslie, Karen; Kafshgari, Morteza Hasanzadeh; Rammes, Gerhard; Ballmann, Markus; Schlegel, Martin; Foulds, Gemma Ann; Pockley, Alan Graham; Schmidt-Graf, Friederike; Multhoff, Gabriele

doi:10.3390/biomedicines11123235

2023

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Title:: 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.
Document type:: Journal Article
Author(s):: Lennartz, Philipp; Thölke, Dennis; Bashiri Dezfouli, Ali; Pilz, Mathias; Lobinger, Dominik; Messner, Verena; Zanth, Hannah; Ainslie, Karen; Kafshgari, Morteza Hasanzadeh; Rammes, Gerhard; Ballmann, Markus; Schlegel, Martin; Foulds, Gemma Ann; Pockley, Alan Graham; Schmidt-Graf, Friederike; Multhoff, Gabriele
Abstract:: 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. «
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 multip... »
Journal title abbreviation:: Biomedicines
Year:: 2023
Journal volume:: 11
Journal issue:: 12
Fulltext / DOI:: doi:10.3390/biomedicines11123235
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/38137456
TUM Institution:: Klinik für Anästhesiologie (DHM); Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde (Prof. Wollenberg); Klinik und Poliklinik für Neurologie (Prof. Hemmer); Klinik und Poliklinik für RadioOnkologie und Strahlentherapie (Prof. Combs)
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