Circulating programmed death ligand-1 (cPD-L1) in non-small-cell lung cancer (NSCLC)

Abstract

BackgroundThis study aimed at investigating feasibility of programmed death ligand-1 (PD-L1) testing in plasma samples of advanced NSCLC patients receiving first-line treatment, assessing whether circulating (c)PD-L1 levels were modified by the therapy and whether baseline cPD-L1 levels were associated with patients’ clinical responses and survival outcome.MethodsPeripheral blood samples were collected from 16 healthy volunteers and 56 newly diagnosed NSCLC patients before and at 12th week during the course of first-line therapy. The level of PD-L1 was measured in plasma samples using the human (PD-L1/CD274) ELISA kit (CUSABIO, MD, USA). The Mann Whitney test or Fisher’s test were used for comparisons. Survival analysis was performed using Kaplan Meyer method, providing median and p-value.ResultsBaseline median cPD-L1 was 42.21 pg/ml (range 12.00-143.49) in NSCLC patients and 37.81 pg/ml (range 9.73-90.21) in healthy control cohort (p = 0.78). Median cPD-L1 increased in patients treated with first-line chemotherapy (63.20 pg/ml vs 39.34 pg/ml; p = 0.002), with no changes in patients exposed to non-chemotherapy drugs (42.39 pg/ml vs 50.67 pg/ml; p = 0.398). Time to progression and overall survival were 4.4 vs 6.9 months (p = 0.062) and 8.8 vs 9.3 months (p = 0.216) in cPD-L1 positive vs cPD-L1 negative patients. Baseline cPD-L1 levels increased with the ascending number of metastatic sites, even if the association was not statistically significant (p = 0.063).ConclusionsThis study showed that cPD-L1 testing is feasible, with chemotherapy influencing PD-L1 plasma levels. The possibility of using such test for predicting or monitoring the effect of immunotherapy or combination of chemotherapy and immunotherapy warrant further investigations.

Liquid biopsy in the era of immuno-oncology: is it ready for prime-time use for cancer patients?

“…Vecchiarelli et al [116] 151 melanoma patients sPD-L1 exists as several variants that can originate from both tumor and immune cells sPD-L1 may serve as a practical dynamic biomarker for the prediction of durable efficacy to immunotherapy agents.…”

Precision Medicine for NSCLC in the Era of Immunotherapy: New Biomarkers to Select the Most Suitable Treatment or the Most Suitable Patient

“…In order to overcome some of the limits of PD-L1 IHC testing, such as tissue unavailability for molecular testing in up to 30% of NSCLC patients [45] and spatial/temporal heterogeneity of IHC expression [46], some studies evaluated soluble PD-L1 (sPD-L1) or PD-L1 expression in Circulating Tumor Cells (CTCs) as an alternative source for PD-L1 evaluation as well as a dynamic biomarker in patients treated with conventional treatments [47][48][49] and/or ICIs [50][51][52][53][54]. High baseline levels of sPD-L1, assessed by an Enzyme Linked Immunosorbent Assay (ELISA), is a poor prognostic factor in lung cancer and seems associated with lower response to PD-1 blockage [55].…”

“…However, changes of sPD-L1 during ICIs have been associated with conflicting results [54]. Interestingly, some data suggest that first line chemotherapy (e.g., platinum and pemetrexed) could significantly increase sPD-L1 median level from baseline, while targeted therapies do not appear to modify sPD-L1 level [47].…”

Pemetrexed Enhances Membrane PD-L1 Expression and Potentiates T Cell-Mediated Cytotoxicity by Anti-PD-L1 Antibody Therapy in Non-Small-Cell Lung Cancer

“…Recent data described discordant results on the predictive and prognostic significance of sPD-L1 in lung cancer patients [25], and the ability of sPD-L1 to interact with its ligand PD-1 on T cells is still on debate. Nevertheless, PD-L1 plasma levels were significantly enhanced in NSCLC patients receiving standard first-line chemotherapy [8] and our data indicated that pemetrexed, as a single regimen, can increase sPD-L1 in plasma patients.…”

“…The regulation of PD-L1 expression is very complex, varying among different tumor types and including both transcriptional and post-transcriptional mechanisms of control [8]. To unravel the mechanisms of pemetrexed-mediated upregulation of PD-L1, we compared the effects of IFN-γ and pemetrexed on intracellular signaling pathways.…”