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PD‐L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer

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Introduction: Therapeutic antibodies to immune checkpoints show promising results. Programmed death‐ligand 1 (PD‐L1), an immune checkpoint ligand, blocks the cancer immunity cycle by binding the PD‐L1 receptor (programmed death 1).… Click to show full abstract

Introduction: Therapeutic antibodies to immune checkpoints show promising results. Programmed death‐ligand 1 (PD‐L1), an immune checkpoint ligand, blocks the cancer immunity cycle by binding the PD‐L1 receptor (programmed death 1). We investigated PD‐L1 protein expression and messenger RNA (mRNA) levels in SCLC. Methods: PD‐L1 protein expression and mRNA levels were determined by immunohistochemistry (IHC) with SP142 and Dako 28‐8 PD‐L1 antibodies and in situ hybridization in primary tumor tissue microarrays in both tumor cells and tumor‐infiltrating immune cells (TIICs) obtained from a limited‐disease SCLC cohort of 98 patients. An additional cohort of 96 tumor specimens from patients with extensive‐disease SCLC was assessed for PD‐L1 protein expression in tumor cells with Dako 28‐8 antibody only. Results: The overall prevalence of PD‐L1 protein expression in tumor cells was 16.5%. In the limited‐disease cohort, the prevalences of PD‐L1 protein expression in tumor cells with SP142 and Dako 28‐8 were 14.7% and 19.4% (tumor proportion score cutoff ≥1%) and PD‐L1 mRNA ISH expression was positive in 15.5% of tumor samples. Increased PD‐L1 protein/mRNA expression was associated with the presence of more TIICs (p < 0.05). The extensive‐disease cohort demonstrated a 14.9% positivity of PD‐L1 protein expression in tumor cells with Dako 28‐8 antibody. Conclusions: A subset of SCLCs is characterized by positive PD‐L1 and/or mRNA expression in tumor cells. Higher PD‐L1 and mRNA expression correlate with more infiltration of TIICs. The prevalence of PD‐L1 in SCLC is lower than that published for NSCLC. The predictive role of PD‐L1 expression in SCLC treatment remains to be established.

Keywords: protein expression; expression tumor; tumor cells; mrna; expression; tumor

Journal Title: Journal of Thoracic Oncology
Year Published: 2017

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