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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-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients
A D'Incecco1, M Andreozzi2, V Ludovini3
1Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital, Viale Alfieri 36, 57124 Livorno, Italy.
Background:
Agents targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) are showing promising results in non-small-cell lung cancer (NSCLC). It is unknown whether PD-1/PD-L1 are differently expressed in oncogene-addicted NSCLC.
Methods:
We analysed a cohort of 125 NSCLC patients, including 56 EGFR mutated, 29 KRAS mutated, 10 ALK translocated and 30 EGFR/KRAS/ALK wild type. PD-L1 and PD-1 expression were assessed by immunohistochemistry. All cases with moderate or strong staining (2+/3+) in >5% of tumour cells were considered as positive.
Results:
PD-1 positive (+) was significantly associated with current smoking status (P=0.02) and with the presence of KRAS mutations (P=0.006), whereas PD-L1+ was significantly associated to adenocarcinoma histology (P=0.005) and with presence of EGFR mutations (P=0.001). In patients treated with EGFR tyrosine kinase inhibitors (N=95), sensitivity to gefitinib or erlotinib was higher in PD-L1+ vs PD-L1 negative in terms of the response rate (RR: P=0.01) time to progression (TTP: P<0.0001) and survival (OS: P=0.09), with no difference in PD1+ vs PD-1 negative. In the subset of 54 EGFR mutated patients, TTP was significantly longer in PD-L1+ than in PD-L1 negative (P=0.01).
Conclusions:
PD-1 and PD-L1 are differentially expressed in oncogene-addicted NSCLC supporting further investigation of specific checkpoint inhibitors in combination with targeted therapies.
Insights
Programmed death-1 ligand (PD-L1) expression differs in non-small-cell lung cancer (NSCLC) with oncogenic mutations. PD-L1 positivity correlates with EGFR mutations and improved response to targeted therapies in NSCLC patients.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Programmed death-1 receptor (PD-1) and its ligand (PD-L1) inhibitors show promise in non-small-cell lung cancer (NSCLC).
- Differential expression of PD-1/PD-L1 in oncogene-addicted NSCLC remains unclear.
Purpose of the Study:
- To investigate the differential expression of PD-1 and PD-L1 in NSCLC based on oncogenic mutations.
- To assess the correlation between PD-1/PD-L1 expression and clinical outcomes in patients receiving targeted therapies.
Main Methods:
- Analysis of a cohort of 125 NSCLC patients, stratified by EGFR, KRAS, ALK mutations, or wild-type status.
- Immunohistochemical assessment of PD-1 and PD-L1 expression, with positivity defined as moderate/strong staining in >5% of tumor cells.
- Correlation of PD-1/PD-L1 expression with smoking status, histology, and mutation status; evaluation of treatment response in patients receiving EGFR tyrosine kinase inhibitors.
Main Results:
- PD-1 positivity associated with smoking and KRAS mutations.
- PD-L1 positivity associated with adenocarcinoma histology and EGFR mutations.
- In EGFR-mutated patients treated with TKIs, PD-L1 positivity correlated with higher response rates, longer time to progression, and improved survival.
Conclusions:
- PD-1 and PD-L1 exhibit differential expression patterns in oncogene-addicted NSCLC.
- Findings support further investigation of checkpoint inhibitors combined with targeted therapies for NSCLC.
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