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Updated: Oct 5, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
PD-L1 tumor expression is associated with poor prognosis and systemic immunosuppression in glioblastoma
Carolina Noronha1,2, Ana Sofia Ribeiro2, Ricardo Taipa3,4
1Neurosurgery Department, Hospital de Santo Antonio, Centro Hospitalar Universitario do Porto, Porto, Portugal.
Purpose:
Glioblastoma is the most common primary malignant brain tumor in the adult, whose grim prognosis largely relates to the absence of effective treatment targets. Given its success in other cancers, immunotherapy has been trialed in glioblastoma and failed to demonstrate the expected benefit. Importantly, these disappointing results highlight the importance of understanding the unique and transforming biology of glioblastoma and its microenvironment. Our goal was to evaluate and characterize the expression of PD-L1 through immunohistochemistry in a large glioblastoma cohort. We further studied PD-L1 expression-associated prognosis and its correlation to systemic and neuropathological parameters.
Methods:
A series of 352 glioblastoma specimens (313 initial resection, 39 matched recurrences) was collected, with a detailed characterization of tumor neuropathological characteristics, including the presence, density and location of tumor infiltrating lymphocytes (TIL). Two hematological markers, absolute lymphocyte count and neutrophil-lymphocyte ratio (NLR), were used to analyze and correlate with systemic inflammation and immunosuppression. Immunohistochemistry was performed to evaluate PD-L1 expression.
Results:
Membranous PD-L1 expression was identified in 31% (98/313) of newly diagnosed and 46% (18/39) of matched recurrent tumors. TIL were found in 26% (82/313) of primary tumors and both density and location were found to be significantly associated with PD-L1 expression (p < 0.001). Interestingly, PD-L1 expressing tumors had more frequently areas with sarcomatous differentiation (p < 0.001) and were significantly associated with lower lymphocyte count (p = 0.018) and higher NLR ratio (p = 0.004) upon diagnosis. Importantly, PD-L1 expression was an independent poor prognostic marker in our cohort.
Conclusion:
Taken together, our data points to a putative role for PD-L1 expression in glioblastoma biology, which correlates to poor patient overall survival, as well as with a general systemic inflammatory status and immunosuppression.
Insights
Programmed death-ligand 1 (PD-L1) expression in glioblastoma correlates with poor prognosis and indicates a systemic inflammatory status. This finding is crucial for understanding glioblastoma biology and developing new therapeutic strategies.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Biology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with poor outcomes.
- Immunotherapy has shown limited success in GBM, necessitating a deeper understanding of its tumor microenvironment.
- Programmed death-ligand 1 (PD-L1) is a key immune checkpoint molecule implicated in tumor immune evasion.
Purpose of the Study:
- To investigate the expression of PD-L1 in a large cohort of glioblastoma patients.
- To analyze the correlation between PD-L1 expression and neuropathological features.
- To determine the prognostic significance of PD-L1 expression in glioblastoma.
Main Methods:
- Immunohistochemistry was used to assess PD-L1 expression in 352 glioblastoma specimens (primary and recurrent).
- Tumor-infiltrating lymphocytes (TILs), absolute lymphocyte count, and neutrophil-lymphocyte ratio (NLR) were analyzed.
- Statistical methods were employed to correlate PD-L1 expression with clinical and pathological parameters.
Main Results:
- PD-L1 expression was detected in 31% of primary and 46% of recurrent glioblastomas.
- PD-L1 expression was significantly associated with the presence and location of TILs, sarcomatous differentiation, lower lymphocyte counts, and higher NLR.
- PD-L1 expression emerged as an independent predictor of poor overall survival.
Conclusions:
- PD-L1 expression plays a role in glioblastoma biology and is linked to a poor prognosis.
- PD-L1 expression in glioblastoma is associated with systemic inflammation and immunosuppression.
- These findings highlight PD-L1 as a potential therapeutic target and biomarker in glioblastoma management.
