Elsevier

Laboratory Investigation

Volume 94, Issue 1, January 2014, Pages 107-116
Laboratory Investigation

Article
Programmed death ligand-1 expression in non-small cell lung cancer

https://doi.org/10.1038/labinvest.2013.130Get rights and content
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Abstract

Recent strategies targeting the interaction of the programmed cell death ligand-1 (PD-L1, B7-H1, CD274) with its receptor, PD-1, resulted in promising activity in early phase clinical trials. In this study, we used various antibodies and in situ mRNA hybridization to measure PD-L1 in non-small cell lung cancer (NSCLC) using a quantitative fluorescence (QIF) approach to determine the frequency of expression and prognostic value in two independent populations. A control tissue microarray (TMA) was constructed using PD-L1-transfected cells, normal human placenta and known PD-L1-positive NSCLC cases. Only one of four antibodies against PD-L1 (5H1) validated for specificity on this TMA. In situ PD-L1 mRNA using the RNAscope method was similarly validated. Two cohorts of NSCLC cases in TMAs including 340 cases from hospitals in Greece and 204 cases from Yale University were assessed. Tumors showed PD-L1 protein expression in 36% (Greek) and 25% (Yale) of the cases. PD-L1 expression was significantly associated with tumor-infiltrating lymphocytes in both cohorts. Patients with PD-L1 (both protein and mRNA) expression above the detection threshold showed statistically significant better outcome in both series (log-rank P=0.036 and P=0.027). Multivariate analysis showed that PD-L1 expression was significantly associated with better outcome independent of histology. Measurement of PD-L1 requires specific conditions and some commercial antibodies show lack of specificity. Expression of PD-L1 protein or mRNA is associated with better outcome. Further studies are required to determine the value of this marker in prognosis and prediction of response to treatments targeting this pathway.

NSCLC
PD-L1
survival
tumor-infiltrating lymphocytes

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Supplementary Information accompanies the paper on the Laboratory Investigation website

Programmed death ligand-1 (PDL1) is a key mechanism of immune evasion in human cancers, and PD-L1 expression on cancer cells may predict response to anti-PD1 therapy. This paper describes a reproducible method of measuring PD-L1 protein and mRNA in formalin-fixed paraffin-embedded samples and demonstrates the prognostic relevance of these biomarkers in non-small cell lung cancer.

Supplementary information The online version of this article (doi:10.1038/labinvest.2013.130) contains supplementary material, which is available to authorized users.

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Vamsidhar Velcheti and Kurt A Schalper: These authors contributed equally to this work.