[HTML][HTML] PD-L1 expression by two complementary diagnostic assays and mRNA in situ hybridization in small cell lung cancer

H Yu, C Batenchuk, A Badzio, TA Boyle… - Journal of Thoracic …, 2017 - Elsevier
H Yu, C Batenchuk, A Badzio, TA Boyle, P Czapiewski, DC Chan, X Lu, D Gao, K Ellison…
Journal of Thoracic Oncology, 2017Elsevier
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 …
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.
Elsevier