Innate and adaptive immune responses following PD‐L1 blockade in treating chronic murine alveolar echinococcosis

Abstract Background Programmed death‐1 (PD‐1) and programmed death ligand‐1 (PD‐L1) immune checkpoint blockade are 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 tre...

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Veröffentlicht in:Parasite Immunology. - 43(2021), 8
1. Verfasser: Jebbawi, Fadi (VerfasserIn)
Weitere Verfasser: Bellanger, Anne‐Pauline, Lunström‐Stadelmann, Britta, Rufener, Reto, Dosch, Michel, Goepfert, Christine, Gottstein, Bruno, Millon, Laurence, Grandgirard, Denis, Leib, Stephen L., Beldi, Guido, Wang, Junhua
Format: Online-Aufsatz
Veröffentlicht: 2021
Zugriff auf das übergeordnete Werk:Parasite Immunology
Umfang:11
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520 |a Abstract Background Programmed death‐1 (PD‐1) and programmed death ligand‐1 (PD‐L1) immune checkpoint blockade are 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 5 d/wk, 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 restore 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. 
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700 1 |a Lunström‐Stadelmann, Britta  |4 aut 
700 1 |a Rufener, Reto  |4 aut 
700 1 |a Dosch, Michel  |4 aut 
700 1 |a Goepfert, Christine  |4 aut 
700 1 |a Gottstein, Bruno  |4 aut 
700 1 |a Millon, Laurence  |4 aut 
700 1 |a Grandgirard, Denis  |4 aut 
700 1 |a Leib, Stephen L.  |4 aut 
700 1 |a Beldi, Guido  |4 aut 
700 1 |a Wang, Junhua  |4 aut 
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