Abstract
We investigated the role of soluble PD-L1 (sPD-L1) in non-small cell lung carcinoma (NSCLC) patients treated with immune checkpoint inhibitors (ICI) and analyzed its association with clinical outcomes and metabolic parameters by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT). Between July 2017 and May 2019, we enrolled 20 candidate patients of ICI therapy who had serum frozen samples and 18F-FDG PET/CT available, both at baseline and at the first response evaluation. This analysis is embedded into a larger prospective study (NCT03563482). Twelve out of 20 patients received nivolumab, one patient received combination of nivolumab and ipilimumab, whereas the others received pembrolizumab. Median sPD-L1 level at baseline was 27.22 pg/mL. We found a significant association between patients with elevated sPD-L1, above the median value, and high metabolic tumor burden, expressed by metabolic tumor volume (MTV, 115.3 vs. 35.5, p = 0.034) and total lesion glycolysis (TLG, 687 vs. 210.1, p = 0.049). At the first restaging after 7–8 weeks, median sPD-L1 levels significantly increased as compared to baseline median value (43.9 pg/mL, p = 0.017). No significant differences in response rates were detected, according to both morphological and metabolic response criteria. Likewise, no difference in survival outcomes were observed between low sPD-L1 and high sPD-L1 patients. The increase of sPD-L1 concentrations during ICI treatment may reflect the expansion of tumor volume and the tumor lysis. Moreover, it is supposed that sPD-L1 has its own biological action, either by reducing membrane PD-1 sites available for nivolumab or by inducing lymphocytes exhaustion after binding their membrane PD-1. Further, larger studies are needed to confirm our preliminary results on the role of sPD-L1 during ICI therapy.
Highlights
Lung cancer is the first cause of cancer-related death worldwide, with a poor prognosis especially in the advanced stages [1]
Most of immune checkpoint inhibitors (ICI) approved so far are based on progression disease (PD)-L1 cell surface expression, its effective predictive value remains under debate due to tumor heterogeneity and lack of standardized effective predictive value remains under debate due to tumor heterogeneity and lack of standardized methods
We showed in addition a significant variation of median soluble PD-L1 (sPD-L1) after three or four cycles of ICI, which was consistent with previous studies [22,23]
Summary
Lung cancer is the first cause of cancer-related death worldwide, with a poor prognosis especially in the advanced stages [1]. The advent of immune checkpoint inhibitors (ICI). Has broaden therapeutic options available for oncologists. By blocking programmed cell death (PD-1)/programmed death ligand (PD-L1) interaction or other checkpoints, e.g., cytotoxic. T-lymphocyte-associated protein 4 (CTLA-4), ICI restore immune surveillance against malignant cells. Cancers 2020, 12, 1373 and improve clinical responses and survival in many tumor types [2,3]. Only a small portion of patients benefit from these new therapies. Beside tumor-tissue biomarkers, such as membrane PD-L1 expression and mutational burden, the identification of potential blood-based biomarkers has attracted the attention of medical community The research for reliable predictive factors discriminating responders from non-responders is a priority, it is still scarce and under debate [4,5].
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