P53 and NLR could recognize distinct subtypes of lung adenocarcinoma with high expression of PD-L1 (TPS≥50%) defined by 22C3

Background: Lung adenocarcinoma (LuAD) with high expression of PD-L1 (TPS≥50%) is a distinct subset of NSCLC and a potential candidate for immunotherapy. Improved understanding of the heterogeneity of PD-L1 high LuAD and recognizing novel biomarkers combined with PD-L1 would facilitate more precise use of PD-1 inhibitors in clinical practice. Methods: Surgically resected tumor tissues from 69 LuAD patients with PD-L1 TPS≥50% defined by 22C3 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 fluorescence in situ hybridization (FISH) assay and TP53 gene mutation was sequenced using Sanger sequencing. Results: The differences of clinicopathological features, including age and spread through air space (STAS), were observed among PD-L1 higher-expression (TPS≥50%，<70%) and highest-expression (TPS≥70%) patients. LuAD with PD-L1 TPS≥70%, aberrant expression of p53 protein or NLR<5 had more expression of IFN-γ protein and higher densities of CD8-positive tumor infiltrating lymphocytes (TILs) as well as Granzyme B -positive T cells comparing with TPS＜70%, p53 protein normal expression or NLR≥5 patients. Conclusions: The present study firstly revealed that distinct subsets could be identified in PD-L1 high LuAD according to p53 protein expression and NLR level, presenting as different characteristics of tumor microenvironment associated with response to PD-1 inhibitors.