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Updated: Nov 5, 2025
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Expression and Prognostic Value of the Immune Checkpoints Galectin-9 and PD-L1 in Glioblastomas
Arnon Møldrup Knudsen1,2, Sisse Josephine Rudkjøbing1,2, Mia Dahl Sørensen1,2
1From the Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
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.
Insights
Galectin-9 and PD-L1 immune checkpoints are present in all glioblastomas (GBMs). Co-expression suggests potential for multi-targeted immune checkpoint inhibition in GBM treatment.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Research
Background:
- Immunotherapy targeting the PD-1/PD-L1 axis shows limited efficacy in glioblastomas (GBMs).
- Compensatory immune checkpoints may contribute to treatment resistance in GBM.
- Galectin-9 is an immune checkpoint protein implicated in T-cell exhaustion and apoptosis.
Purpose of the Study:
- To investigate the expression and co-expression of Galectin-9 and PD-L1 in GBM.
- To explore the potential of Galectin-9 as a therapeutic target in GBM.
Main Methods:
- Immunohistochemical staining for Galectin-9 and PD-L1 in 163 IDH wildtype GBM samples.
- Software-based quantitation of protein expression.
- Double immunofluorescence for co-expression analysis.
Main Results:
- Both Galectin-9 and PD-L1 were expressed in all 163 GBM tumors.
- A significant positive correlation was observed between Galectin-9 and PD-L1 expression (p=0.0017).
- Co-expression of Galectin-9 and PD-L1 was found in 88.3% of tumors, on both tumor cells and microglia/macrophages.
Conclusions:
- Galectin-9 and PD-L1 are ubiquitously expressed in GBM, with frequent co-expression.
- The co-expression of Galectin-9 and PD-L1 provides a rationale for developing multi-targeted immune checkpoint inhibition strategies for GBM.
