Circulating levels of PD-L1 and tumor metabolism correlate to patients outcome in surgically resected NSCLC

Objectives: The level of soluble PD-L1 is reported as a prognostic factor in different tumor types. Herein we evaluate the clinical-pathological and prognostic significance of circulating PD-L1 level in patients with surgically treated NSCLC, by combining data with tissue expression of PD-L1 and other immune-related markers, as well as with the metabolic parameters measured by 18F-FDG PET/CT.

Methods: Patients with resected NSCLC (n=40; stage IA-IIIA), having a pre-operative blood storage in the institutional biobank, and undergoing staging 18F-FDG PET/CT less than 45 days before surgery, were enrolled for the current study. In all cases, we determined plasma levels of PD-L1 (pg/ml), immune reactive areas (IRA%) covered by CD3-TILs, CD68-TAMs, CD20 B cells and CD8-TILs, PD-1 and PD-L1 in tumor specimen, as well as metabolic parameters: i.e. SUVmax, SUVpeak, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Variables were statistically analyzed and associated to disease-free survival (DFS).

Results: The circulating PD-L1 in the blood stream could be determined in 38 out of the 40 (95%) samples. The mean and median expression levels were 34.86pg/ml and 24.83pg/ml, respectively. On statistical analysis, the circulating and tissue expression of PD-L1 resulted independent from each other. Some degree of positive correlation was determined between tissue PD-L1 and SUVmax (rho=0.390; p=0.0148). Hierarchical clustering combining circulating, tissue and metabolic parameters identified clusters of patients with high metabolic tumor burden or high expression of plasma PD-L1 levels (Z-score≥2) as having a poor DFS (p= 0.033). This cluster model resulted significant also on univariate analysis, whereas multivariate analysis detected stage and metabolism (i.e. SUVmax and SUVpeak) as independent prognostic factors to DFS.

Conclusions: The plasma levels of PD-L1 result independent from its expression in NSCLC tumor tissue and, when combined with tumor metabolism and other clinical-pathological parameters, allow for the identification of clusters of patients with different outcome.