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Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
PD-L1 and PD-L2 expression correlated genes in non-small-cell lung cancer
Trine Vilsbøll Larsen1, Dianna Hussmann1, Anders Lade Nielsen2
1Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
Background:
Programmed cell death ligand-1 (PD-L1) and ligand-2 (PD-L2) interaction with programmed cell death protein-1 (PD-1) represent an immune-inhibiting checkpoint mediating immune evasion and is, accordingly, an important target for blockade-based immunotherapy in cancer. In non-small-cell lung cancer (NSCLC), improved understanding of PD-1 checkpoint blockade-responsive biology and identification of biomarkers for prediction of a clinical response to immunotherapy is warranted. Thus, in the present study, we systematically described PD-L1 and PD-L2 expression correlated genes in NSCLC.
Methods:
We performed comparative retrospective analyses to identify PD-L1 and PD-L2 mRNA expression correlated genes in NSCLC. For this, we examined available datasets from the cancer cell line encyclopedia (CCLE) project lung non-small-cell (Lung_NSC) and the cancer genome atlas (TCGA) projects lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC).
Results:
Analysis of the CCLE dataset Lung_NSC identified expression correlation between PD-L1 and PD-L2. Moreover, we identified expression correlation between 489 genes and PD-L1, 191 genes and PD-L2, and 111 genes for both. PD-L1 and PD-L2 also expression correlated in TCGA datasets LUAD and LUSC. In LUAD, we identified expression correlation between 257 genes and PD-L1, 914 genes and PD-L2, and 211 genes for both. In LUSC, we identified expression correlation between 26 genes and PD-L1, 326 genes and PD-L2, and 13 genes for both. Only a few genes expression correlated with PD-L1 and PD-L2 across the CCLE and TCGA datasets. Expression of Interferon signaling-involved genes converged in particular with the expression correlated genes for PD-L1 in Lung_NSC, for PD-L2 in LUSC, and for both PD-L1 and PD-L2 in LUAD. In LUSC, PD-L1, and to a lesser extent PD-L2, expression correlated with chromosome 9p24 localized genes, indicating a chromosome 9p24 topologically associated domain as an important driver of in particular LUSC PD-L1 expression. Expression correlation analyses of the PD-L1 and PD-L2 receptors programmed cell death protein-1 (PD-1), Cluster of differentiation 80 (CD80), and Repulsive guidance molecule B (RGMB) showed that PD-1 and CD80 expression correlated with both PD-L1 and PD-L2 in LUAD. CD80 expression correlated with PD-L2 in LUSC.
Conclusions:
We present gene signatures associated with PD-L1 and PD-L2 mRNA expression in NSCLC which could possess importance in relation to understand PD-1 checkpoint blockade-responsive biology and development of gene signature based biomarkers for predicting clinical responses to immunotherapy.
Insights
This study identifies gene signatures correlated with PD-L1 and PD-L2 expression in non-small-cell lung cancer (NSCLC). These findings may aid in understanding immunotherapy response and developing predictive biomarkers for cancer treatment.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Programmed cell death ligand-1 (PD-L1) and ligand-2 (PD-L2) interactions with programmed cell death protein-1 (PD-1) are key immune checkpoints in cancer.
- Understanding PD-1 blockade response and identifying predictive biomarkers in non-small-cell lung cancer (NSCLC) is crucial for effective immunotherapy.
Purpose of the Study:
- To systematically describe genes correlated with PD-L1 and PD-L2 mRNA expression in NSCLC.
- To identify potential gene signatures for predicting response to PD-1 checkpoint blockade immunotherapy.
Main Methods:
- Comparative retrospective analyses of PD-L1 and PD-L2 mRNA expression correlated genes.
- Utilized datasets from the Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) projects for NSCLC, lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC).
Main Results:
- Identified significant gene expression correlations with PD-L1 and PD-L2 across CCLE and TCGA datasets.
- Discovered convergence of Interferon signaling-involved genes with PD-L1/PD-L2 expression, particularly in LUAD.
- Observed correlation of PD-L1 expression with chromosome 9p24 genes in LUSC, suggesting its role in driving PD-L1 expression.
Conclusions:
- Presented novel gene signatures associated with PD-L1 and PD-L2 mRNA expression in NSCLC.
- These signatures hold potential for understanding PD-1 checkpoint blockade-responsive biology.
- Findings may facilitate the development of gene signature-based biomarkers for predicting immunotherapy clinical response.
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