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Clinical significance of ? 50% PD-L1 expression with the SP263 monoclonal antibody in non-small cell lung cancer patients.

ABSTRACT: BACKGROUND:PD-L1 expression in tumor cells has been associated with the efficacy of immune checkpoint inhibitors in non-small cell lung cancer (NSCLC). The aim of this study was to explore correlations between smoking, genetic profiles, patient outcomes, and PD-L1 expression in NSCLC. METHODS:PD-L1 expression was evaluated in 241 surgically resected specimens by immunostaining and 50% was set as the cutoff value. RESULTS:Of the 241 tumors analyzed, a PD-L1 tumor proportion score (TPS) of ? 50% was detected in 35 cases (14.5%) and a TPS of < 50% in 206 cases (85.5%). A PD-L1 TPS ? 50% was significantly associated with smoking and EGFR wild-type status (P < 0.001 and P = 0.039, respectively). Detailed assessment of smoking variables showed that total smoking duration was a predictor of a PD-L1 TPS ? 50% (P = 0.001). Univariate and multivariate survival analyses revealed that patients with a PD-L1 TPS ? 50% had poorer disease-free and overall survival than those with a PD-L1 TPS < 50% (P = 0.001 and P < 0.001, respectively). CONCLUSION:The incidence of a PD-L1 TPS ? 50% was significantly higher in smoking and EGFR wild-type NSCLC patients, particularly in long-term smokers. A PD-L1 TPS of ? 50% was an independent adverse prognostic factor for survival in patients with NSCLC.

SUBMITTER: Li W

PROVIDER: S-EPMC6360219 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Clinical significance of ≥ 50% PD-L1 expression with the SP263 monoclonal antibody in non-small cell lung cancer patients.

Li Wenbin W Song Peng P Guo Lei L Liu Xiuyun X Guo Changyuan C Ying Jianming J Gao Shugeng S

Thoracic cancer 20181211 2

<h4>Background</h4>PD-L1 expression in tumor cells has been associated with the efficacy of immune checkpoint inhibitors in non-small cell lung cancer (NSCLC). The aim of this study was to explore correlations between smoking, genetic profiles, patient outcomes, and PD-L1 expression in NSCLC.<h4>Methods</h4>PD-L1 expression was evaluated in 241 surgically resected specimens by immunostaining and 50% was set as the cutoff value.<h4>Results</h4>Of the 241 tumors analyzed, a PD-L1 tumor proportion ...[more]

PMID: 30536734

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Project description:BackgroundProgrammed 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.MethodsWe 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).ResultsAnalysis 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.ConclusionsWe 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.

Dataset Information

Clinical significance of ? 50% PD-L1 expression with the SP263 monoclonal antibody in non-small cell lung cancer patients.

Publications

Clinical significance of ≥ 50% PD-L1 expression with the SP263 monoclonal antibody in non-small cell lung cancer patients.

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