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Assessment of the PD-L1 status by immunohistochemistry: challenges and perspectives for therapeutic strategies in lung cancer patients

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Abstract

Immunotherapy targeting the PD-L1/PD-1 axis has recently shown spectacular efficacy and promise for the future of patients with metastatic lung cancer. In the setting of second-line treatment of metastatic disease, this therapy has increased overall survival of patients by several months when compared to chemotherapy, both for squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the lung. Clinical trials targeting the PD-1/PD-L1 axis have shown a tendency towards higher efficacy if expression of PD-L1 is relatively high, as evaluated by immunohistochemistry (IHC) of tumour samples. Targeting the PD-1/PD-L1 axis is of crucial importance not only for metastatic non-small cell lung cancer (NSCLC) but probably also for patients with small cell lung cancer. Nivolumab, an antibody targeting PD-1, has recently received FDA and EMA approval for NSCLC, regardless of the PDL1 expression status (for both tumour types in the USA and for only SCC in EU). However, the need for a biomarker that allows better selection of patients is essential, to improve treatment efficacy and to manage cost of these therapies. Assessment of PD-L1 expression through immunohistochemical staining is advocated by many as one such potential biomarker. This prospect raises several questions, in particular how to define a threshold for positive PD-L1 labelling on biopsy tissue samples, taking into account that certain patients respond to treatment targeting PD-L1/PD-1, despite low or absent immunoreactivity of this biomarker. This review discusses major challenges related to detection of PD-L1 by immunohistochemistry as a companion diagnostic test, along with immune checkpoint blockade treatment of lung cancer.

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Authors and Affiliations

  1. Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, University of Nice Sophia Antipolis, 30 avenue de la voie romaine, 06002, Nice, France

    Marius Ilie, Véronique Hofman & Paul Hofman

  2. Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081 and UMR CNRS 7284, Team 3, CLCC Antoine Lacassagne, Nice, France

    Marius Ilie, Véronique Hofman & Paul Hofman

  3. Hospital-Integrated Biobank BB-0033-00025, Pasteur Hospital, Nice, France

    Marius Ilie, Véronique Hofman & Paul Hofman

  4. University Hospital Federation OncoAge, CHU de Nice, University of Nice Sophia Antipolis, Nice, France

    Marius Ilie, Véronique Hofman & Paul Hofman

  5. Institute of Pathology, Humboldt University of Berlin, Berlin, Germany

    Manfred Dietel

  6. Campus Charité Mitte, Charité Universitätsmedizin, Berlin, Germany

    Manfred Dietel

  7. Drug Development Department (DITEP), Gustave Roussy, Villejuif, France

    Jean-Charles Soria

  8. INSERM U981, Predictive Biomarkers and New Therapeutic Strategies in Oncology, University Paris Sud, Gustave Roussy, Villejuif, France

    Jean-Charles Soria

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  1. Marius Ilie
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  2. Véronique Hofman
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  3. Manfred Dietel
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  4. Jean-Charles Soria
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  5. Paul Hofman
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Corresponding author

Correspondence to Paul Hofman.

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Conflict of interest

Paul Hofman is a member of several industry scientific advisory boards for which he receives a speaker honorarium. Manfred Dietel is a member of several industry sponsored advisory boards for which he receives a speaker honorarium. JC Soria has received consultancy fees from MSD, AstraZeneca, Roche-Genentech and Pfizer. Véronique Hofman and Marius Ilié declare that they have no conflict of interest.

Additional information

Marius Ilie and Véronique Hofman contributed equally to this work.

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Ilie, M., Hofman, V., Dietel, M. et al. Assessment of the PD-L1 status by immunohistochemistry: challenges and perspectives for therapeutic strategies in lung cancer patients. Virchows Arch 468, 511–525 (2016). https://doi.org/10.1007/s00428-016-1910-4

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  • DOI: https://doi.org/10.1007/s00428-016-1910-4

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