Abstract
BackgroundImmune checkpoint inhibitors (ICIs) have become a high-profile regimen for malignancy recently. However, only a small subpopulation obtains long-term clinical benefit. How to select optimal patients by reasonable biomarkers remains a hot topic.MethodsPaired tissue samples and blood samples from 51 patients with advanced malignancies were collected for correlation analysis. Dynamic changes in blood PD-L1 (bPD-L1) expression, including PD-L1 mRNA, exosomal PD-L1 (exoPD-L1) protein and soluble PD-L1 (sPD-L1), were detected after 2 months of ICIs treatment in advanced non-small-cell lung cancer (NSCLC) patients. The best cutoff values for progression-free survival (PFS) and overall survival (OS) of all three biomarkers were calculated with R software.ResultsIn 51 cases of various malignancies, those with positive tissue PD-L1 (tPD-L1) had significantly higher PD-L1 mRNA than those with negative tPD-L1. In 40 advanced NSCLC patients, those with a fold change of PD-L1 mRNA ≥ 2.04 had better PFS, OS and best objective response (bOR) rate. In addition, a fold change of exoPD-L1 ≥ 1.86 was also found to be associated with better efficacy and OS in a cohort of 21 advanced NSCLC cases. The dynamic change of sPD-L1 was not associated with efficacy and OS. Furthermore, the combination of PD-L1 mRNA and exoPD-L1 could screen better patients for potential benefit from ICIs treatment.ConclusionThere was a positive correlation between bPD-L1 and tPD-L1 expression. Increased expression of PD-L1 mRNA, exoPD-L1, or both in early stage of ICIs treatment could serve as positive biomarkers of efficacy and OS in advanced NSCLC patients.
Highlights
Immune checkpoint inhibitors (ICIs) treatment has become an increasingly high-profile regimen for malignancies since 2013
There was a trend that patients with positive tissue progressive disease (PD)-L1 (tPD-L1) expression had higher programmed cell death ligand 1 (PD-L1) mRNA expression (Figure 1A)
Our results demonstrated that patients with positive tPD-L1 expression had higher PD-L1 mRNA and soluble PD-L1 (sPD-L1) expression in plasma, which demonstrated that bPD-L1 expression had a positive correlation with tPD-L1 expression at the same timepoints
Summary
Immune checkpoint inhibitors (ICIs) treatment has become an increasingly high-profile regimen for malignancies since 2013. Patients with malignancies obtain remarkable survival benefits from ICIs treatment, for example, when antibodies against programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are compared to traditional chemotherapy in non-small-cell lung cancer (NSCLC) [1, 2]. Using single or multiple biomarkers to select patients who could benefit from ICIs was the focus in the current study. The detection of pretreatment PD-L1 protein expression on TCs or ICs by immunohistochemistry (IHC) is the most frequently used predictive biomarker in clinical practice. Previous studies KEYNOTE 024 and IMpower 110 have demonstrated that NSCLC patients with higher tPD-L1 expression could obtain better clinical benefits, including objective response rate (ORR), progression-free survival (PFS) and OS [12, 13]. How to select optimal patients by reasonable biomarkers remains a hot topic
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