부산대학교 도서관

Aims To study programmed death ligand 1 ( PD-L1) expression, tumour-infiltrating T lymphocytes ( TILs) and the molecular context in patients with early-stage squamous cell lung carcinomas ( SCCs). Methods and results The study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early-stage SCC. PD-L1 immunohistochemistry ( IHC) was performed with three commercially available clones (E1L3N, SP263 and SP142). CD8+ TILs were scored with a digital algorithm. All tumours were analysed with targeted next-generation sequencing ( NGS). Additionally, TP53 mutations were investigated with direct sequencing. In both cohorts, we observed a significant association between CD8+ TILs density and high PD-L1 IHC expression in tumour cells ( TCs). Furthermore, high SP142 PD-L1 expression in immune cells ( ICs) was also associated significantly with CD8+ TILs density. Therefore, CD8+ TILs density discriminated between patients with high versus low PD-L1 IHC expression with excellent sensitivity and specificity. Interestingly, the highest percentages of PD-L1-positive TCs with the three antibodies were found in samples with cyclin-dependent kinase 6 ( CDK6) amplification, with high amplification of proto-oncogene C-Myc ( CMYC) or with cyclin D1- PI3 kinase subunit alpha ( CCND1- PIK3 CA) co-amplification. High SP142 PD-L1 IHC expression in ICs showed a non-significant correlation with TP53 mutations. Conversely, most cases with fibroblast growth factor receptor 1 ( FGFR1) amplification were negative for all PD-L1 clones. Conclusions Our preliminary results support the use of digital CD8+ TILs scoring and targeted NGS alongside PD-L1 expression. The approach presented herein could help define patients with SCCs candidates to immune checkpoints inhibitors. [ABSTRACT FROM AUTHOR]