Back to Search
Start Over
Absence of PD-L1 expression on tumor cells in the context of an activated immune infiltrate may indicate impaired IFN gamma signaling in non-small cell lung cancer
- Source :
- PLoS One, 14, 5, PLoS ONE, 14(5):e0216864. Public Library of Science, PLoS One, 14, PLoS ONE, 14(5). Public Library of Science, PLoS ONE, Vol 14, Iss 5, p e0216864 (2019), PLoS ONE
- Publication Year :
- 2019
-
Abstract
- BackgroundIn non-small cell lung cancer (NSCLC), PD-L1 expression on either tumor cells (TC) or both TC and tumor-infiltrating immune cells (IC) is currently the most used biomarker in cancer immunotherapy. However, the mechanisms involved in PD-L1 regulation are not fully understood. To provide better insight in these mechanisms, a multiangular analysis approach was used to combine protein and mRNA expression with several clinicopathological characteristics.Patients and methodsArchival tissues from 640 early stage, resected NSCLC patients were analyzed with immunohistochemistry for expression of PD-L1 and CD8 infiltration. In addition, mutational status and expression of a selection of immune genes involved in the PD-L1/PD-1 axis and T-cell response was determined.ResultsTumors with high PD-L1 expression on TC or on IC represent two subsets of NSCLC with minimal overlap. We observed that PD-L1 expression on IC irrespective of expression on TC is a good marker for inflammation within tumors. In the tumors with the highest IC expression and absent TC expression an association with reduced IFNγ downstream signaling in tumor cells was observed.ConclusionsThese results show that PD-L1 expression on TC and IC are both independent hallmarks of the inflamed phenotype in NSCLC, and TC-negative/IC-high tumors can also be categorized as inflamed. The lack of correlation between PD-L1 TC and IC expression in this subgroup may be caused by impaired IFNγ signaling in tumor cells. These findings may bring a better understanding of the tumor-immune system interaction and the clinical relevance of PD-L1 expression on IC irrespective of PD-L1 expression on TC.
- Subjects :
- Male
Lung Neoplasms
medicine.medical_treatment
Protein Expression
Programmed Cell Death 1 Receptor
Gene Expression
CD8-Positive T-Lymphocytes
Biochemistry
Lung and Intrathoracic Tumors
B7-H1 Antigen
0302 clinical medicine
Cancer immunotherapy
Carcinoma, Non-Small-Cell Lung
Cellular types
Gene expression
Medicine and Health Sciences
Cytotoxic T cell
030212 general & internal medicine
Immune Response
Aged, 80 and over
Regulation of gene expression
Immunity, Cellular
Insertion Mutation
Multidisciplinary
Agricultural and Biological Sciences(all)
Immune cells
Middle Aged
Neoplasm Proteins
Gene Expression Regulation, Neoplastic
Oncology
030220 oncology & carcinogenesis
White blood cells
Medicine
Immunohistochemistry
Female
Research Article
Signal Transduction
Adult
Cell biology
Blood cells
Science
Immunology
T cells
Cytotoxic T cells
Biology
Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9]
Research and Analysis Methods
Interferon-gamma
03 medical and health sciences
Immune system
All institutes and research themes of the Radboud University Medical Center
Genetics
Gene Expression and Vector Techniques
medicine
Journal Article
Humans
Molecular Biology Techniques
Lung cancer
Molecular Biology
Immunohistochemistry Techniques
Aged
Neoplasm Staging
Molecular Biology Assays and Analysis Techniques
Biochemistry, Genetics and Molecular Biology(all)
Biology and Life Sciences
Cancers and Neoplasms
medicine.disease
Non-Small Cell Lung Cancer
Histochemistry and Cytochemistry Techniques
Animal cells
Mutation
Immunologic Techniques
Cancer research
Biomarkers
CD8
Genetics and Molecular Biology(all)
Subjects
Details
- ISSN :
- 19326203
- Database :
- OpenAIRE
- Journal :
- PLoS One, 14, 5, PLoS ONE, 14(5):e0216864. Public Library of Science, PLoS One, 14, PLoS ONE, 14(5). Public Library of Science, PLoS ONE, Vol 14, Iss 5, p e0216864 (2019), PLoS ONE
- Accession number :
- edsair.doi.dedup.....56c9e935a597303c8ca691ca860f905c