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Title: Characterization of PD-1 upregulation on tumor-infiltrating lymphocytes in human and murine gliomas and preclinical therapeutic blockade
Authors: Dejaegher, Joost ×
Verschuere, Tina
Vercalsteren, Ellen
Boon, Louis
Cremer, Jonathan
Sciot, Raf
Van Gool, Stefaan W
De Vleeschouwer, Steven #
Issue Date: Nov-2017
Publisher: Wiley-Liss
Series Title: International Journal of Cancer vol:141 issue:9 pages:1891-1900
Article number: 10.1002/ijc.30877
Abstract: Blockade of the immune checkpoint molecule programmed-cell-death-protein-1 (PD-1) yielded promising results in several cancers. To understand the therapeutic potential in human gliomas, quantitative data describing the expression of PD-1 are essential. Moreover, due the immune-specialized region of the brain in which gliomas arise, differences between tumor-infiltrating and circulating lymphocytes should be acknowledged. In this study we have used flow cytometry to quantify PD-1 expression on tumor-infiltrating T cells of 25 freshly resected glioma cell suspensions (10 newly and 5 relapsed glioblastoma, 10 lower grade gliomas) and simultaneously isolated circulating T cells. A strong upregulation of PD-1 expression in the tumor microenvironment compared to the blood circulation was seen in all glioma patients. Additionally, circulating T cells were isolated from 15 age-matched healthy volunteers, but no differences in PD-1 expression were found compared to glioma patients. In the murine GL261 malignant glioma model, there was a similar upregulation of PD-1 on brain-infiltrating lymphocytes. Using a monoclonal PD-1 blocking antibody, we found a marked prolonged survival with 55% of mice reaching long-term survival. Analysis of brain-infiltrating cells 21 days after GL261 tumor implantation showed a shift in infiltrating lymphocyte subgroups with increased CD8+ T cells and decreased regulatory T cells. Together, our results suggest an important role of PD-1 in glioma-induced immune escape, and provide translational evidence for the use of PD-1 blocking antibodies in human malignant gliomas.
URI: 
ISSN: 0020-7136
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
Molecular and Vascular Biology
Research Group Experimental Neurosurgery and Neuroanatomy
× corresponding author
# (joint) last author

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