title: Assessment of the PD-L1 status by immunohistochemistry: challenges and perspectives for therapeutic strategies in lung cancer patients.
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.
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, University of Nice Sophia Antipolis, 30 avenue de la voie romaine, 06002, Nice, France.|Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081 and UMR CNRS 7284, Team 3, CLCC Antoine Lacassagne, Nice, France.|Hospital-Integrated Biobank BB-0033-00025, Pasteur Hospital, Nice, France.|University Hospital Federation OncoAge, CHU de Nice, University of Nice Sophia Antipolis, Nice, France.
authors.forename: Marius
authors.initials: M
authors.lastname: Ilie
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, University of Nice Sophia Antipolis, 30 avenue de la voie romaine, 06002, Nice, France.|Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081 and UMR CNRS 7284, Team 3, CLCC Antoine Lacassagne, Nice, France.|Hospital-Integrated Biobank BB-0033-00025, Pasteur Hospital, Nice, France.|University Hospital Federation OncoAge, CHU de Nice, University of Nice Sophia Antipolis, Nice, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Hofman
authors.affiliation: Institute of Pathology, Humboldt University of Berlin, Berlin, Germany.|Campus Charité Mitte, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.|INSERM U981, Predictive Biomarkers and New Therapeutic Strategies in Oncology, University Paris Sud, Gustave Roussy, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, University of Nice Sophia Antipolis, 30 avenue de la voie romaine, 06002, Nice, France. hofman.p@chu-nice.fr.|Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081 and UMR CNRS 7284, Team 3, CLCC Antoine Lacassagne, Nice, France. hofman.p@chu-nice.fr.|Hospital-Integrated Biobank BB-0033-00025, Pasteur Hospital, Nice, France. hofman.p@chu-nice.fr.|University Hospital Federation OncoAge, CHU de Nice, University of Nice Sophia Antipolis, Nice, France. hofman.p@chu-nice.fr.
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D061026:Programmed Cell Death 1 Receptor
keywords: Diagnostic pitfalls; Immunohistochemistry; Immunotherapy; Lung cancer; PD-1; PD-L1