Jacobs, Joannes F. M. and Idema, Albert J. and Bol, Kalijn F. and Nierkens, Stefan and Grauer, Oliver M. and Wesseling, Pieter and Grotenhuis, J. Andre and Hoogerbrugge, Peter M. and de Vries, I. Jolanda M. and Adema, Gosse J. (2009) Regulatory T cells and the PD-L1/PD-1 pathway mediate immune suppression in malignant human brain tumors. NEURO-ONCOLOGY, 11 (4). pp. 394-402. ISSN 1522-8517, 1523-5866
Full text not available from this repository. (Request a copy)Abstract
The brain is a specialized immune site representing a unique tumor microenvironment. The availability of fresh brain tumor material for ex vivo analysis is often limited because large parts of many brain tumors are resected using ultrasonic aspiration. We analyzed ultrasonic tumor aspirates as a biosource to study immune suppressive mechanisms in 83 human brain tumors. Lymphocyte infiltrates in brain tumor tissues and ultrasonic aspirates were comparable with respect to lymphocyte content and viability. Applying ultrasonic aspirates, we detected massive infiltration of CD4(+)FoxP3(+)CD25(high) CD127(low) regulatory T cells (Tregs) in glioblastomas (n = 29) and metastatic brain tumors (n = 20). No Treg accumulation was observed in benign tumors such as meningiomas (n = 10) and pituitary adenomas (n = 5). A significant Treg increase in blood was seen only in patients with metastatic brain tumors. Tregs in high-grade tumors exhibited an activated phenotype as indicated by decreased proliferation and elevated CTLA-4 and FoxP3 expression relative to blood Tregs. Functional analysis showed that the tumor-derived Tregs efficiently suppressed cytokine secretion and proliferation of autologous intratumoral lymphocytes. Most tumor-infiltrating Tregs were localized in close proximity to effector T cells, as visualized by immunohistochemistry. Furthermore, 61% of the malignant brain tumors expressed programmed death ligand-1 (PD-L1), while the inhibitory PD-1 receptor was expressed on CD4(+) effector cells present in 26% of tumors. In conclusion, using ultrasonic tumor aspirates as a biosource we identified Tregs and the PD-L1/PD-1 pathway as immune suppressive mechanisms in malignant but not benign human brain tumors. Neuro-Oncology 11, 394-402, 2009 (Posted to Neuro-Oncology [serial online], Doc. D08-00138, November 21, 2008. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-104)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CENTRAL-NERVOUS-SYSTEM; IN-VIVO; EXPRESSION; GLIOMA; FOXP3; VACCINATION; EXPANSION; SURVIVAL; MICROENVIRONMENT; IMMUNOTHERAPY; brain tumor; immunotherapy; PD-L1; regulatory T cell; tumor-infiltrating lymphocyte |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Sep 2020 08:29 |
| Last Modified: | 10 Sep 2020 08:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28660 |
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