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
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Biomedicines - 11(2023), 12 vom: 07. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lennartz, Philipp [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 25.12.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/biomedicines11123235 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366281143 |
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| 100 | 1 | |a Lennartz, Philipp |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Biomarkers in Adult-Type Diffuse Gliomas |b 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 |
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| 520 | |a 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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| 700 | 1 | |a Thölke, Dennis |e verfasserin |4 aut | |
| 700 | 1 | |a Bashiri Dezfouli, Ali |e verfasserin |4 aut | |
| 700 | 1 | |a Pilz, Mathias |e verfasserin |4 aut | |
| 700 | 1 | |a Lobinger, Dominik |e verfasserin |4 aut | |
| 700 | 1 | |a Messner, Verena |e verfasserin |4 aut | |
| 700 | 1 | |a Zanth, Hannah |e verfasserin |4 aut | |
| 700 | 1 | |a Ainslie, Karen |e verfasserin |4 aut | |
| 700 | 1 | |a Kafshgari, Morteza Hasanzadeh |e verfasserin |4 aut | |
| 700 | 1 | |a Rammes, Gerhard |e verfasserin |4 aut | |
| 700 | 1 | |a Ballmann, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Schlegel, Martin |e verfasserin |4 aut | |
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| 700 | 1 | |a Schmidt-Graf, Friederike |e verfasserin |4 aut | |
| 700 | 1 | |a Multhoff, Gabriele |e verfasserin |4 aut | |
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