Periphery TH/TS ratio and TP53 mutation predict the efficacy of ICI-based therapy in advanced non-small cell lung cancer with high PD-L1 expression

Background High programmed death-ligand 1 (PD-L1) expression represents a clinically meaningful improvement in survival benefit after administration of immune checkpoint inhibitors (ICIs). It remains that only a minority of patients with PD-L1 high expression demonstrate durable response in a real-life setting. The study aimed to explore the correlation between dynamic changes of lymphocyte subpopulations and clinical responses in non-small cell lung cancer (NSCLC) by integrating genomic profiling. Experimental Design : Patients with PD-L1 ≥ 50% advanced NSCLC were classified into durable clinical benefit (DCB) and no durable benefit (NDB) groups according to radio-graphical evaluation. Flow cytometry was employed to analyse the dynamic changes of lymphocytes “before” and “after” therapy. Results 119 patients were included and patients who exerted durable response to ICI-directed therapy had significantly higher circulating CD4 + T cell ( p  = 0.0006), CD8 + T cell ( p  = 0.0043), and TH/TS ratio ( p  = 0.0018) compared to NDB group. Using 1.735 as optimal cut-off value, the sensitivity and specificity of TH/TS ratio for predicting treatment response were 0.9118 and 0.8000, respectively. The median progression-free survival (PFS) was significantly longer in patients with higher value of TH/TS. Pre-treatment gene mutational analyses were performed in 69 patients, TP53-exon 7 mutation with TH/TS < 1.735 showed a significantly shorter PFS compared with other subgroups. Conclusions The value of TH/TS acts as a reliable predictor to individual response with PD-L1 high expression, and the lower value of TH/TS combined with TP53-exon7 mutation contribute to unsatisfactory treatment effects.