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Expression, prognostic significance and therapeutic implications of PD-L1 in gliomas
Gayaththri Vimalathas1, Bjarne Winther Kristensen1,2,3
1Department of Pathology, Odense University Hospital, Odense, Denmark.
Abstract:
The advent of checkpoint immunotherapy, particularly with programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors, has provided ground-breaking results in several advanced cancers. Substantial efforts are being made to extend these promising therapies to other refractory cancers such as gliomas, especially glioblastoma, which represents the most frequent and malignant glioma and carries an exceptionally grim prognosis. Thus, there is a need for new therapeutic strategies with related biomarkers. Gliomas have a profoundly immunosuppressive tumour micro-environment and evade immunological destruction by several mechanisms, one being the expression of inhibitory immune checkpoint molecules such as PD-L1. PD-L1 is recognised as an important therapeutic target and its expression has been shown to hold prognostic value in different cancers. Several clinical trials have been launched and some already completed, but PD-1/PD-L1 inhibitors have yet to show convincing clinical efficacy in gliomas. Part of the explanation may reside in the vast molecular heterogeneity of gliomas and a complex interplay within the tumour micro-environment. In parallel, critical knowledge about PD-L1 expression is beginning to accumulate including knowledge on expression levels, testing methodology, co-expression with other checkpoint molecules and prognostic and predictive value. This article reviews these aspects and points out areas where biomarker research is needed to develop more successful checkpoint-related therapeutic strategies in gliomas.
Insights
Checkpoint immunotherapy using PD-1/PD-L1 inhibitors shows promise in advanced cancers but faces challenges in gliomas. Further biomarker research is crucial for developing effective glioma treatment strategies.
Area of Science:
- Oncology
- Immunology
- Neuro-oncology
Background:
- Checkpoint immunotherapy, including PD-1/PD-L1 inhibitors, has revolutionized cancer treatment.
- Gliomas, particularly glioblastoma, remain challenging due to their immunosuppressive micro-environment and poor prognosis.
- PD-L1 expression is a key immune evasion mechanism and a potential therapeutic target in gliomas.
Purpose of the Study:
- To review current knowledge on PD-L1 expression in gliomas.
- To identify the challenges and opportunities for PD-1/PD-L1 inhibitor efficacy in glioma treatment.
- To highlight areas for future biomarker research to improve therapeutic strategies.
Main Methods:
- Review of existing literature on PD-1/PD-L1 inhibitors in glioma treatment.
- Analysis of PD-L1 expression patterns, testing methodologies, and prognostic/predictive value.
- Discussion of glioma heterogeneity and tumor micro-environment interactions.
Main Results:
- PD-1/PD-L1 inhibitors have not yet demonstrated convincing clinical efficacy in gliomas.
- Glioma's molecular heterogeneity and complex tumor micro-environment contribute to treatment resistance.
- Accumulating knowledge on PD-L1 expression, including levels, testing, and co-expression, is critical.
Conclusions:
- PD-L1 is a significant target, but its role in glioma requires further elucidation.
- Overcoming resistance necessitates a deeper understanding of glioma biology and immune interactions.
- Targeted biomarker research is essential for advancing checkpoint inhibitor therapies in gliomas.
