Aligning digital CD8+ scoring and targeted next‐generation sequencing with programmed death ligand 1 expression: a pragmatic approach in early‐stage squamous cell lung carcinoma

• DOI: 10.1111/his.13346
• Publication Date: 2017-08-17T07:58:02Z
• Authors: Esther Conde; Alejandra Caminoa; Carolina Dominguez; Antonio Calles; Stefan Walter; Barbara Angulo; Elena Sánchez; Marta Alonso; Luis Jimenez; Luis Madrigal; Florentino Hernando; Julian Sanz‐Ortega; Beatriz Jimenez; Pilar Garrido; Luis Paz‐Ares; Javier de Castro; Susana Hernandez; Fernando Lopez‐Rios
• Keywords: Adult; Male; Lung Neoplasms; High-Throughput Nucleotide Sequencing; Kaplan-Meier Estimate; CD8-Positive T-Lymphocytes; Middle Aged; Proto-Oncogene Mas; B7-H1 Antigen; Disease-Free Survival; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; 0302 clinical medicine; Image Interpretation, Computer-Assisted; Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Female; Aged

AimsTo 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 resultsThe 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–PIK3CA) 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.ConclusionsOur 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.