[The circulating PD-L1: An emerging predictive biomarker for immune checkpoint inhibitors response]. / Le taux circulant de PD-L1 : un biomarqueur émergent de réponse aux inhibiteurs de checkpoints immunitaires.

Immune checkpoint inhibitors (ICI) have recently become the standard of care for many metastatic solid tumors, with considerable improvements in patient prognosis. However, a non-negligible proportion of patients does not respond to this type of treatment, making it essential to identify predictive factors of this response in order to better adapt the therapy. Among the biomarkers that have been most extensively studied in recent years, tumor PD-L1 levels come out on top, with controversial results for predicting response to ICI. The determination of circulating PD-L1 (or soluble PD-L1) in peripheral blood seems to be an interesting emerging biomarker. Indeed, several studies have investigated its prognostic value, and/or its potential predictive value of response to immunotherapy, and it would appear that there is a correlation between the level of soluble PD-L1 and the level of tumor aggressiveness and therefore prognosis. Furthermore, the results suggest that higher PD-L1 levels are associated with a poorer response to immunotherapy, although this remains to be confirmed in large-scale studies.

Clinical significance of tumoral PD-L1 expression in Wilms tumors.

BACKGROUND: Although cure rate for Wilms tumor (WT) is high recent years, there is still small fraction of patients suffering from tumor relapse or metastases. It is urgent to identify more valuable biomarkers associated with disease progression. Previous studies have shown that PD-L1 was abnormally expressed in various type of cancers and acted as predictor for poor prognosis for those cancers. PD-1/PD-L1 inhibitors have achieved great success in various malignancies with correlation between PD-L1 expression and responses. We conducted this retrospective study to better understand the role of PD-L1 in WT development. OBJECTIVE: The aim of this study was to evaluate the expression rate of tumoral PD-L1 in WT and investigate the association of PD-L1 with tumor invasion and metastasis. STUDY DESIGN: Seventy-seven patients with WT, including 20 cases of primary WTs with corresponding resected invasive/lymph node metastatic tumors were enrolled in the research. Immunohistochemistry was used to examine tumoral PD-L1 expression. Kaplan-Meier analysis with regard to the relationship between the expression of tumoral PD-L1 and follow-up information was performed. RESULTS: Positive expression rate of tumoral PD-L1 was 28.6% in primary WT tissues, while 35% in associated invasive/metastatic ones. The tumoral PD-L1 expression in primary WTs were correlated with late stage and unfavorable histology (P = 0.007; P = 0.002). The expression rate of tumoral PD-L1 was higher in the progression group than that without distant metastasis or relapse (P = 0.038). The expression rate of PD-L1 between primary WTs and matched invasive/metastatic tissues was concordant (P = 0.435). Tumoral PD-L1 expression was associated with disease-free survival (DFS) and overall survival (OS) (P = 0.02; P = 0.03). Tumor PD-L1 expression was associated with DFS and OS in univariable analyses but not in multivariable Cox regression, adjusting for histology and tumor stage. DISCUSSION: We found that PD-L1 expression was associated with the late-stage of WT and unfavorable histology, which were tightly associated with disease relapse and progression, predicting poor prognosis. The subsequent survival analysis also showed that PD-L1 expression was linked to both shorter DFS and OS. After adjustment for WT stage and histology, PD-L1 expression was no longer an independent predictor of DFS/OS. The value of PD-L1 as predictor for prognosis and potential therapeutic target in WT still need to be validated in large cohort in future. CONCLUSION: Although PD-L1 expression correlated with established prognostic factors in our dataset, its value as a prognostic marker and therapeutic target, if any, remains to be shown in future.

Negative Correlation Between 18F-RGD Uptake via PET and Tumoral PD-L1 Expression in Non-Small Cell Lung Cancer.

Purpose: We investigated the correlation of 18F-AlF-NOTAPRGD2 (18F-RGD) uptake during positron emission tomography (PET) with tumoral programmed death-ligand 1 (PD-L1) expression and explored its potential in immune checkpoint inhibitor treatment. Methods: Forty-two mice were subcutaneously injected with CMT-167 lung carcinoma cells. A total of 30 mice with good growth tumor and good general condition were selected. 18F-RGD PET scanning was performed on days 0, 2, 4, 6, 9, and 11 with five mice per day. Immunohistochemistry (IHC) for PD-L1 was performed on each specimen obtained from tumors. Thirty patients with advanced non-small cell lung cancer (NSCLC) were scanned using 18F-RGD PET/CT, and Milliplex multifactor detection analyzed serum PD-1/PD-L1 expression of twenty-eight of them. Thirteen of them were analyzed immunohistochemically using core needle biopsy samples obtained from primary tumors. Results: Thirty mice were scanned by 18F-RGD PET/CT and analyzed for PD-L1 expression in tumor cells by IHC finally. Maximum standard uptake value (SUVmax) and mean SUV (SUVmean) were significantly lower in relatively-higher-PD-L1-expression tumors than in relatively-low-PD-L1-expression tumors (P < 0.05). In patients, the SUVmax was significantly negatively correlated with tumoral PD-L1 expression by IHC (P=0.014). SUVmean, peak SUV (SUVpeak), and gross tumor volume (GTV) were also negatively correlated with PD-L1, but without significance (P > 0.05). SUVmax, SUVmean, SUVpeak, and GTV were negatively correlated with serum PD-1 and PD-L1, but not significantly. According to the receiver operating characteristic curve analysis, significant correlations between SUVmax and tumoral PD-L1 expression in both mice and patients were present (P < 0.05). Conclusion: Higher 18F-RGD uptake is correlated with depressed PD-L1 expression in tumor cells, and SUVmax is the best parameter to display tumoral expression of PD-L1. 18F-RGD PET may be useful for reflecting the immune status of NSCLC.