Aligning Digital CD8+ Scoring and Targeted Next-Generation Sequencing with PD-L1 Expression: A Pragmatic Approach in Early-Stage Squamous Cell Lung Carcinoma

Abstract

Aims

To study 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 analyzed 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 significantly associated 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 CDK6 amplification, with high amplification of CMYC or with CCND1-PIK3CA co-amplification. High SP142 PD-L1 IHC expression in ICs showed a non-significant correlation with TP53 mutations. Conversely, most cases with 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.

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