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Updated: Feb 28, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Assessment of programmed death-ligand 1 expression and tumor-associated immune cells in pediatric cancer tissues
Robbie G Majzner1, Jason S Simon2, Joseph F Grosso2
1Department of Pediatrics, Stanford University, Stanford, California.
Background:
Programmed death 1 (PD-1) signaling in the tumor microenvironment dampens immune responses to cancer, and blocking this axis induces antitumor effects in several malignancies. Clinical studies of PD-1 blockade are only now being initiated in pediatric patients, and little is known regarding programmed death-ligand 1 (PD-L1) expression in common childhood cancers. The authors characterized PD-L1 expression and tumor-associated immune cells (TAICs) (lymphocytes and macrophages) in common pediatric cancers.
Methods:
Whole slide sections and tissue microarrays were evaluated by immunohistochemistry for PD-L1 expression and for the presence of TAICs. TAICs were also screened for PD-L1 expression.
Results:
Thirty-nine of 451 evaluable tumors (9%) expressed PD-L1 in at least 1% of tumor cells. The highest frequency histotypes comprised Burkitt lymphoma (80%; 8 of 10 tumors), glioblastoma multiforme (36%; 5 of 14 tumors), and neuroblastoma (14%; 17 of 118 tumors). PD-L1 staining was associated with inferior survival among patients with neuroblastoma (P = .004). Seventy-four percent of tumors contained lymphocytes and/or macrophages. Macrophages were significantly more likely to be identified in PD-L1-positive versus PD-L1-negative tumors (P < .001).
Conclusions:
A subset of diagnostic pediatric cancers exhibit PD-L1 expression, whereas a much larger fraction demonstrates infiltration with tumor-associated lymphocytes. PD-L1 expression may be a biomarker for poor outcome in neuroblastoma. Further preclinical and clinical investigation will define the predictive nature of PD-L1 expression in childhood cancers both at diagnosis and after exposure to chemoradiotherapy. Cancer 2017;123:3807-3815. © 2017 American Cancer Society.
Insights
Programmed death-ligand 1 (PD-L1) is expressed in some pediatric cancers, particularly Burkitt lymphoma and neuroblastoma. PD-L1 expression may indicate a poorer prognosis in neuroblastoma patients.
Area of Science:
- Immunology
- Pediatric Oncology
- Cancer Research
Background:
- Programmed death 1 (PD-1) signaling suppresses anti-cancer immune responses.
- Blocking PD-1 shows promise in adult malignancies.
- PD-1 ligand (PD-L1) expression in pediatric cancers is largely uncharacterized.
Purpose of the Study:
- To assess programmed death-ligand 1 (PD-L1) expression in pediatric tumors.
- To identify tumor-associated immune cells (TAICs) in these cancers.
- To correlate PD-L1 expression with patient survival.
Main Methods:
- Immunohistochemistry used to evaluate PD-L1 expression on whole slide sections and tissue microarrays.
- TAICs (lymphocytes and macrophages) identified and screened for PD-L1.
- Statistical analysis performed to assess correlations.
Main Results:
- PD-L1 expression detected in 9% of 451 pediatric tumors.
- Highest frequencies in Burkitt lymphoma (80%), glioblastoma (36%), and neuroblastoma (14%).
- PD-L1 positivity associated with inferior survival in neuroblastoma (P=.004).
- Lymphocytes/macrophages present in 74% of tumors; macrophages more common in PD-L1-positive tumors.
Conclusions:
- A subset of pediatric cancers express PD-L1, while many show immune cell infiltration.
- PD-L1 expression may serve as a negative prognostic biomarker in neuroblastoma.
- Further research needed to clarify PD-L1's predictive role in childhood cancers.
