Review
. 2018 Apr; 10:1758835918763493.
doi: 10.1177/1758835918763493.

PD-L1 expression testing in non-small cell lung cancer

Cristina Teixidó 1 Noelia Vilariño 2 Roxana Reyes 3 Noemí Reguart 4 
Affiliations
  • PMID: 29662547
  •     64 References
  •     51 citations

Abstract

In recent years, immunotherapy has revolutionized and changed the standard of care in patients with advanced non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors, fundamentally those that act by blocking the programmed cell death receptor-1 (PD-1) and its ligand the programmed cell death ligand-1 (PD-L1) have emerged as novel treatment strategies in NSCLC, demonstrating undoubted superiority over chemotherapy in terms of efficacy. Several of these immune checkpoint modulators have recently gained regulatory approval for the treatment of advanced NSCLC, such as nivolumab, atezolizumab and pembrolizumab in first-line (only the latter) and second-line settings, and more recently, durvalumab as maintenance after chemoradiotherapy in locally advanced disease. There is consensus that PD-L1 expression on tumor cells predicts responsiveness to PD-1 inhibitors in several tumor types. Hence PD-L1 expression evaluated by immunohistochemistry (IHC) is currently used as a clinical decision-making tool to support the use of checkpoint inhibitors in NSCLC patients. However, the value of PD-L1 as the 'definitive' biomarker is controversial as its testing is puzzled by multiple unsolved issues such as the use of different staining platforms and antibodies, the type of cells in which PD-L1 is assessed (tumor versus immune cells), thresholds used for PD-L1-positivity, or the source and timing for sample collection. Therefore, newer biomarkers such as tumor mutation burden and neoantigens as well as biomarkers reflecting host environment (microbiome) or tumor inflamed microenvironment (gene expression signatures) are being explored as more reliable and accurate alternatives to IHC for guiding treatment selection with checkpoint inhibitors in NSCLC.

Keywords: PD-L1 expression testing; immunohistochemistry (IHC); immunotherapy; non-small cell lung cancer (NSCLC); predictive biomarker.

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Cancers (Basel), 2021 May 01; 13(9). PMID: 33923116    Free PMC article.
Simple parameters to solve a complex issue: predicting response to checkpoint inhibitor therapy in lung cancer.
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J Transl Med, 2021 Jun 09; 19(1). PMID: 34098964    Free PMC article.
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Kumar Prabhash, Suresh H Advani, +6 authors, Ashok K Vaid.
Adv Ther, 2019 Mar 14; 36(4). PMID: 30864106
Immune Checkpoint Inhibitors and Cardiotoxicity: An Analysis of Spontaneous Reports in Eudravigilance.
Annamaria Mascolo, Cristina Scavone, +8 authors, Annalisa Capuano.
Drug Saf, 2021 Jun 20; 44(9). PMID: 34145536    Free PMC article.
Current status and quality of radiomic studies for predicting immunotherapy response and outcome in patients with non-small cell lung cancer: a systematic review and meta-analysis.
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Karmele Saez de Gordoa, Ingrid Lopez, +5 authors, Cristina Teixido.
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Therapeutic and Systemic Adverse Events of Immune Checkpoint Inhibitors Targeting the PD-1/PD-L1 axis for Clinical Management of NSCLC.
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Combined Consideration of Tumor-Associated Immune Cell Density and Immune Checkpoint Expression in the Peritumoral Microenvironment for Prognostic Stratification of Non-Small-Cell Lung Cancer Patients.
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