p53 expression and NLR could recognize distinct subtypes of lung adenocarcinoma with high expression of PD-L1...

Lung adenocarcinoma (LUAD) with high expression of PD-L1 (TPS ≥ 50%) is a distinct subset of NSCLC and a potential immunotherapy candidate. An improved understanding of the heterogeneity of PD-L1-high LUAD patients and the recognition of other biomarkers combined with PD-L1 could facilitate more precise use of PD-1 inhibitors in clinical practice.

Surgically resected tumour tissues from 69 LUAD patients with a PD-L1 TPS ≥ 50% defined by 22C3 antibody were tested for p53 and IFN-γ protein expression using immunohistochemistry. The densities of CD8 and Granzyme B-positive T cells were evaluated by immunohistochemistry. EGFR mutation was detected by RT‒PCR, ALK rearrangement was examined by a fluorescence in situ hybridization (FISH) assay, and TP53 gene mutations were sequenced using Sanger sequencing.

Differences in clinicopathological features, including age and spread through the air space (STAS), were observed between patients with higher PD-L1 expression (TPS ≥ 50%, < 70%) and those with the highest PD-L1 expression (TPS ≥ 70%). LUAD patients whose PD-L1 TPS was ≥ 70% and whose p53 protein abnormal expression or NLR was < 5 had higher densities of CD8-positive tumour-infiltrating lymphocytes (TILs) and Granzyme B-positive T cells as well as higher IFN-γ protein expression than those whose TPS was < 70%, those whose p53 protein expression was normal, or those whose NLR was ≥ 5.

The present study is the first to reveal that distinct subtypes of PD-L1-high LUAD can be identified on the basis of p53 protein expression and the NLR. p53 expression and the NLR can recognize a subtype with brisk immune cell cytotoxicity that might potentially respond better to PD-1 inhibitors.