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Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
Published on: September 25, 2018
PD-L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer
Hui Yu1, Cory Batenchuk2, Andrzej Badzio3
1Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Introduction:
Therapeutic antibodies to immune checkpoints show promising results. Programmed death-ligand 1 (PD-L1), an immune checkpoint ligand, blocks the cancer immunity cycle by binding the PD-L1 receptor (programmed death 1). We investigated PD-L1 protein expression and messenger RNA (mRNA) levels in SCLC.
Methods:
PD-L1 protein expression and mRNA levels were determined by immunohistochemistry (IHC) with SP142 and Dako 28-8 PD-L1 antibodies and in situ hybridization in primary tumor tissue microarrays in both tumor cells and tumor-infiltrating immune cells (TIICs) obtained from a limited-disease SCLC cohort of 98 patients. An additional cohort of 96 tumor specimens from patients with extensive-disease SCLC was assessed for PD-L1 protein expression in tumor cells with Dako 28-8 antibody only.
Results:
The overall prevalence of PD-L1 protein expression in tumor cells was 16.5%. In the limited-disease cohort, the prevalences of PD-L1 protein expression in tumor cells with SP142 and Dako 28-8 were 14.7% and 19.4% (tumor proportion score cutoff ≥1%) and PD-L1 mRNA ISH expression was positive in 15.5% of tumor samples. Increased PD-L1 protein/mRNA expression was associated with the presence of more TIICs (p < 0.05). The extensive-disease cohort demonstrated a 14.9% positivity of PD-L1 protein expression in tumor cells with Dako 28-8 antibody.
Conclusions:
A subset of SCLCs is characterized by positive PD-L1 and/or mRNA expression in tumor cells. Higher PD-L1 and mRNA expression correlate with more infiltration of TIICs. The prevalence of PD-L1 in SCLC is lower than that published for NSCLC. The predictive role of PD-L1 expression in SCLC treatment remains to be established.
Insights
Programmed death-ligand 1 (PD-L1) expression was investigated in small cell lung cancer (SCLC). PD-L1 protein and mRNA levels were assessed, revealing a subset of SCLC tumors with positive expression associated with increased immune cell infiltration.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Immune checkpoint inhibitors targeting Programmed death-ligand 1 (PD-L1) have shown therapeutic promise.
- PD-L1 is an immune checkpoint ligand that can inhibit anti-tumor immunity by binding to its receptor, Programmed death 1 (PD-1).
- Understanding PD-L1 expression in small cell lung cancer (SCLC) is crucial for potential immunotherapeutic strategies.
Purpose of the Study:
- To investigate the prevalence of PD-L1 protein and messenger RNA (mRNA) expression in tumor cells and tumor-infiltrating immune cells (TIICs) in patients with SCLC.
- To explore the correlation between PD-L1 expression and the presence of TIICs in SCLC.
- To compare PD-L1 prevalence in SCLC with that reported in non-small cell lung cancer (NSCLC).
Main Methods:
- PD-L1 protein expression was assessed using immunohistochemistry (IHC) with SP142 and Dako 28-8 antibodies.
- PD-L1 mRNA levels were determined by in situ hybridization (ISH).
- Analyses were conducted on tissue microarrays from two SCLC cohorts: one with limited-disease (n=98) and another with extensive-disease (n=96).
Main Results:
- The overall prevalence of PD-L1 protein expression in tumor cells was 16.5%.
- In the limited-disease cohort, PD-L1 protein expression (SP142/Dako 28-8) ranged from 14.7% to 19.4%, and PD-L1 mRNA expression was positive in 15.5% of samples.
- Increased PD-L1 protein/mRNA expression was significantly associated with a higher presence of TIICs (p < 0.05).
Conclusions:
- A subset of SCLC tumors exhibits positive PD-L1 protein and/or mRNA expression.
- Higher PD-L1 expression correlates with increased infiltration of TIICs in SCLC.
- The prevalence of PD-L1 in SCLC appears lower than in NSCLC, and its predictive role in SCLC treatment requires further investigation.
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