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Media type:
E-Article
Title:
Expression and Prognostic Value of the Immune Checkpoints Galectin-9 and PD-L1 in Glioblastomas
Contributor:
Knudsen, Arnon Møldrup;
Rudkjøbing, Sisse Josephine;
Sørensen, Mia Dahl;
Dahlrot, Rikke Hedegaard;
Kristensen, Bjarne Winther
Published:
Oxford University Press (OUP), 2021
Published in:
Journal of Neuropathology & Experimental Neurology, 80 (2021) 6, Seite 541-551
Language:
English
DOI:
10.1093/jnen/nlab041
ISSN:
0022-3069;
1554-6578
Origination:
Footnote:
Description:
Abstract Immunotherapeutic targeting of the PD-1/PD-L1 axis has been widely implemented for treatment of several cancer types but shown disappointing results in glioblastomas (GBMs), potentially due to compensatory mechanisms of other expressed immune checkpoints. Galectin-9 is an immune-checkpoint protein that facilitates T-cell exhaustion and apoptosis and could be a potential target for immune-checkpoint inhibition. A total of 163 GBMs IDH wildtype were immunostained with anti-Galectin-9 and PD-L1 antibodies. Software-based quantitation of immunostainings was performed and co-expression was investigated using double immunofluorescence. Both Galectin-9 and PD-L1 protein expression were found in all 163 tumors and showed a significant positive correlation (p = 0.0017). Galectin-9 expression varied from 0.01% to 32% (mean = 6.61%), while PD-L1 membrane expression ranged from 0.003% to 0.14% (mean = 0.048%) of total tumor area. Expression of Galectin-9 and PD-L1 was found on both microglia/macrophages and tumor cells, and colocalization of both markers was found in 88.3% of tumors. In multivariate analysis, neither Galectin-9 (HR = 0.99), PD-L1 (HR = 1.05), nor their combinations showed prognostic value. Galectin-9 and PD-L1 were expressed in all investigated GBMs and the majority of patients had co-expression, which may provide rationale for multi-targeted immune checkpoint inhibition.