PD-L1 Expression of Lung Cancer Cells,Unlike Infiltrating Immune Cells,Is Stable and Unaffected by Therapy During Brain Metastasis |
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Authors: | Vanda Téglási Orsolya Pipek Rita Lózsa Kinga Berta Dávid Szüts Tünde Harkó Pál Vadász Lívia Rojkó Balázs Döme Attila G Bagó József Tímár Judit Moldvay Zoltán Szállási Lilla Reiniger |
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Institution: | 1. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary;2. Department of Physics of Complex Systems, Eötvös Loránd University, Budapest, Hungary;3. Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary;4. Department of Pathology, National Korányi Institute of Pulmonology, Budapest, Hungary;5. Department of Thoracic Surgery, National Korányi Institute of Pulmonology, Budapest, Hungary;6. VI Department of Pulmonology, National Korányi Institute of Pulmonology, Budapest, Hungary;7. Department of Tumor Biology, National Korányi Institute of Pulmonology–Semmelweis University, Budapest, Hungary;8. Division of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria;9. Department of Neurooncology, National Institute of Clinical Neurosciences, Budapest, Hungary;10. Hungarian Academy of Sciences–Semmelweis University, Molecular Oncology Research Unit, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary;11. SE-NAP Brain Metastasis Research Group, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary;12. Computational Health Informatics Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA;13. Danish Cancer Society Research Center, Copenhagen, Denmark |
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Abstract: | BackgroundApproximately 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 MethodsSurgically 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.ResultsThere 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.ConclusionWe 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. |
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Keywords: | Addresses for correspondence: Lilla Reiniger MD PhD 1st Department of Pathology and Experimental Cancer Research Semmelweis University Üll?i út 26 H-1085 Budapest Hungary Fax: + 36 1 317 1074 Immune checkpoint Immune environment Lung adenocarcinoma Programmed death ligand 1 |
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