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Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
PD-L1 Expression of Lung Cancer Cells, Unlike Infiltrating Immune Cells, Is Stable and Unaffected by Therapy During
Vanda Téglási1, Orsolya Pipek2, Rita Lózsa3
11st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Background:
Approximately 50% of brain metastases originate from non-small-cell lung cancer. The median survival of patients with brain metastases is 1 month without treatment. Novel immunotherapeutic strategies, such as those targeting the programmed death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) axis, are promising in patients with advanced systemic disease but are often preferentially administered to patients with tumors showing PD-L1 positivity.
Patients And Methods:
Surgically resected paired primary lung adenocarcinoma and brain metastasis samples of 61 patients were analyzed. We compared the paired samples regarding the amount of peritumoral and stromal mononuclear infiltration, PD-L1 expression of tumor and immune cells, and PD-1 expression of immune cells. We investigated the effect of radiotherapy, chemotherapy, and steroid therapy on PD-L1 expression in brain metastases.
Results:
There was significant positive correlation regarding the PD-L1 expression of tumor cells between the paired primary lung adenocarcinoma and brain metastatic samples with the use of different cutoff levels (1%, 5%, 50%). We found no impact of chemotherapy or steroid therapy on the changes of PD-L1 expression of tumor cells between the 2 sites. There is no or only limited concordance of the proportion of PD-1- or PD-L1-positive tumor-associated immune cells between the paired tumor samples, which suggests that brain metastases develop their own immune environment.
Conclusion:
We observed a strong correlation of PD-L1 positive tumor cells between primary lung adenocarcinoma cases and their corresponding brain metastases, which is not significantly influenced by chemotherapy or steroid therapy.
Insights
Tumor cell programmed death ligand 1 (PD-L1) expression strongly correlates between primary lung adenocarcinoma and brain metastases. This correlation is unaffected by chemotherapy or steroid therapy, guiding treatment strategies for non-small-cell lung cancer brain metastases.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Research
Background:
- Non-small-cell lung cancer frequently metastasizes to the brain, with poor prognosis.
- Immunotherapies targeting the programmed death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) axis show promise but rely on PD-L1 expression.
- Understanding PD-L1 expression in brain metastases is crucial for effective immunotherapy selection.
Purpose of the Study:
- To compare programmed death ligand 1 (PD-L1) expression in paired primary lung adenocarcinoma and brain metastasis samples.
- To investigate the influence of systemic therapies on PD-L1 expression in brain metastases.
- To analyze the immune microenvironment of brain metastases.
Main Methods:
- Analysis of paired primary lung adenocarcinoma and brain metastasis samples from 61 patients.
- Assessment of PD-L1 expression on tumor and immune cells, and PD-1 expression on immune cells.
- Evaluation of the impact of radiotherapy, chemotherapy, and steroid therapy on PD-L1 expression.
Main Results:
- A significant positive correlation was observed in PD-L1 expression of tumor cells between primary lung adenocarcinoma and brain metastases.
- Chemotherapy and steroid therapy did not impact the changes in tumor cell PD-L1 expression between primary and metastatic sites.
- Limited concordance in PD-1/PD-L1 positive immune cells suggests distinct immune microenvironments in brain metastases.
Conclusions:
- PD-L1 expression on tumor cells is highly correlated between primary lung adenocarcinoma and its brain metastases.
- This correlation is not significantly altered by chemotherapy or steroid therapy.
- Brain metastases may develop unique immune microenvironments independent of the primary tumor's immune infiltrate.
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Published on: September 25, 2018
10:29Semi-automatic PD-L1 Characterization and Enumeration of Circulating Tumor Cells from Non-small Cell Lung Cancer Patients by Immunofluorescence
Published on: August 14, 2019
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