TY - JOUR
T1 - The immunological landscape of peripheral blood in glioblastoma patients and immunological consequences of age and dexamethasone treatment
AU - Dusoswa, Sophie A
AU - Verhoeff, Jan
AU - van Asten, Saskia
AU - Lübbers, Joyce
AU - van den Braber, Marlous
AU - Peters, Sophie
AU - Abeln, Sanne
AU - Crommentuijn, Matheus H W
AU - Wesseling, Pieter
AU - Vandertop, William Peter
AU - Twisk, Jos W R
AU - Würdinger, Thomas
AU - Noske, David
AU - van Kooyk, Yvette
AU - Garcia-Vallejo, Juan J
N1 - Publisher Copyright: Copyright © 2024 Dusoswa, Verhoeff, van Asten, Lübbers, van den Braber, Peters, Abeln, Crommentuijn, Wesseling, Vandertop, Twisk, Würdinger, Noske, van Kooyk and Garcia-Vallejo.
PY - 2024
Y1 - 2024
N2 - BACKGROUND: Glioblastomas manipulate the immune system both locally and systemically, yet, glioblastoma-associated changes in peripheral blood immune composition are poorly studied. Age and dexamethasone administration in glioblastoma patients have been hypothesized to limit the effectiveness of immunotherapy, but their effects remain unclear. We compared peripheral blood immune composition in patients with different types of brain tumor to determine the influence of age, dexamethasone treatment, and tumor volume.METHODS: High-dimensional mass cytometry was used to characterise peripheral blood mononuclear cells of 169 patients with glioblastoma, lower grade astrocytoma, metastases and meningioma. We used blood from medically-refractory epilepsy patients and healthy controls as control groups. Immune phenotyping was performed using FlowSOM and t-SNE analysis in R followed by supervised annotation of the resulting clusters. We conducted multiple linear regression analysis between intracranial pathology and cell type abundance, corrected for clinical variables. We tested correlations between cell type abundance and survival with Cox-regression analyses.RESULTS: Glioblastoma patients had significantly fewer naive CD4+ T cells, but higher percentages of mature NK cells than controls. Decreases of naive CD8+ T cells and alternative monocytes and an increase of memory B cells in glioblastoma patients were influenced by age and dexamethasone treatment, and only memory B cells by tumor volume. Progression free survival was associated with percentages of CD4+ regulatory T cells and double negative T cells.CONCLUSION: High-dimensional mass cytometry of peripheral blood in patients with different types of intracranial tumor provides insight into the relation between intracranial pathology and peripheral immune status. Wide immunosuppression associated with age and pre-operative dexamethasone treatment provide further evidence for their deleterious effects on treatment with immunotherapy.
AB - BACKGROUND: Glioblastomas manipulate the immune system both locally and systemically, yet, glioblastoma-associated changes in peripheral blood immune composition are poorly studied. Age and dexamethasone administration in glioblastoma patients have been hypothesized to limit the effectiveness of immunotherapy, but their effects remain unclear. We compared peripheral blood immune composition in patients with different types of brain tumor to determine the influence of age, dexamethasone treatment, and tumor volume.METHODS: High-dimensional mass cytometry was used to characterise peripheral blood mononuclear cells of 169 patients with glioblastoma, lower grade astrocytoma, metastases and meningioma. We used blood from medically-refractory epilepsy patients and healthy controls as control groups. Immune phenotyping was performed using FlowSOM and t-SNE analysis in R followed by supervised annotation of the resulting clusters. We conducted multiple linear regression analysis between intracranial pathology and cell type abundance, corrected for clinical variables. We tested correlations between cell type abundance and survival with Cox-regression analyses.RESULTS: Glioblastoma patients had significantly fewer naive CD4+ T cells, but higher percentages of mature NK cells than controls. Decreases of naive CD8+ T cells and alternative monocytes and an increase of memory B cells in glioblastoma patients were influenced by age and dexamethasone treatment, and only memory B cells by tumor volume. Progression free survival was associated with percentages of CD4+ regulatory T cells and double negative T cells.CONCLUSION: High-dimensional mass cytometry of peripheral blood in patients with different types of intracranial tumor provides insight into the relation between intracranial pathology and peripheral immune status. Wide immunosuppression associated with age and pre-operative dexamethasone treatment provide further evidence for their deleterious effects on treatment with immunotherapy.
KW - dexamethasone
KW - glioblastoma
KW - immune monitoring
KW - large cohort
KW - mass cytometry
UR - http://www.scopus.com/inward/record.url?scp=85184162495&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2024.1343484
DO - 10.3389/fimmu.2024.1343484
M3 - Article
C2 - 38318180
SN - 1664-3224
VL - 15
SP - 1343484
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1343484
ER -