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BACKGROUND Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) immune checkpoint blockade is efficacious in certain cancer therapies. OBJECTIVES The present study aimed to provide a picture about the development of innate and adaptive immune responses upon PD-L1 blockade in treating chronic murine AE. METHODS Immune treatment started at 6 weeks post E. multilocularis-infection, and was maintained for 8 weeks with twice per week anti-PD-L1 administration (intraperitoneal). The study included an outgroup-control with mice perorally medicated with albendazole five days/week, and another one with both treatments combined. Assessment of treatment efficacy was based on determining parasite weight, innate and adaptive immune cell profiles, histopathology, and liver tissue cytokine levels. RESULTS/CONCLUSIONS Findings showed that the parasite load was significantly reduced in response to PD-L1 blockade, and this blockade a) contributed to T cell activity by increasing CD4+ /CD8+ effector T cells, and decreasing Tregs; b) had the capacity to re-store DCs and Kupffer cells/Macrophages; c) suppressed NKT and NK cells; and thus d) lead to an improved control of E. multilocularis infection in mice. This study suggests that the PD-L1 pathway plays an important role by regulating adaptive and innate immune cells against E. multilocularis infection, with significant modulation of tissue inflammation.

AIMS Alveolar echinococcosis (AE) is characterized by a chronically progressing hepatic injury caused by Echinococcus multilocularis. Surgery presently remains the best curative option. Currently, biological predictive features derived from the resected specimens are not suitable to assess surgery efficacy. The present study was designed to investigate whether a selection of markers measured on the resected specimens exhibits predictive features related to parasite viability, or to a total elimination of the parasite, in addition to serological markers. METHODS AND RESULTS In a collaboration between two centers, one in France (Besancon), and one in Switzerland (Bern), samples from 40 AE patients were analyzed by microarray and serology techniques, individually. Paired serum samples before and after surgery were obtained for 26 patients. In the sera, a significant decrease of PD-L1 levels was observed after surgery, in addition to anti-Em18 levels. In the liver tissue, low levels of Cluster of Differentiation (CD)-3 were correlated with the absence of serum anti-Em18 after surgery. CONCLUSION This study showed PD-L1 is promising as a potential serological marker, and further confirmed the performance of anti-Em18 serology. Further studies on a larger cohort is needed to confirm the utility of performing systematically microarray on resected liver tissue.

AIMS Alveolar echinococcosis is a severe chronic helminthic infection that mimics a tumour-like disease. This study aimed at investigating in vitro interactions between Echinococcus multilocularis vesicular fluid (VF) and different immune checkpoints (PD-1/PD-L1, CTLA-4, LAG-3 and TIM-3). METHODS AND RESULTS Peripheral blood mononuclear cells (PBMC) from healthy blood donors were isolated by Ficoll. Natural killer (NK) cells were selected. Each type of cell was stimulated individually with E. multilocularis-VF. Expression of the different immune checkpoints was measured by flow cytometry on day 3 and day 6; all supernatants were used for immunoassays. Cells and supernatants from 22 healthy donors were analysed. A significant increase of PD-1, PD-L1, LAG-3 and TIM-3 was observed upon E. multilocularis-VF exposure for NK cells on day 3 (P