Immunotherapy of alveolar echinococcosis via PD-1/PD-L1 immune checkpoint blockade in mice.

Wang, Junhua; Jebbawi, Fadi; Bellanger, Anne-Pauline; Beldi, Guido; Millon, Laurence; Gottstein, Bruno (2018). Immunotherapy of alveolar echinococcosis via PD-1/PD-L1 immune checkpoint blockade in mice. Parasite immunology, 40(12), e12596. Blackwell Scientific Publications 10.1111/pim.12596

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The growth potential of the tumour-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly dependent upon the nature/function of the periparasitic adaptive host immune-mediated processes. PD-1/PD-L1 pathway (programmed cell death 1), which inhibits lymphocytic proliferation in tumour development, is over-expressed at the chronic stage of AE. We tested the impact of a PD-1/PD-L1 pathway blockade on the outcome of both chronic AE (intraperitoneal metacestode inoculation, secondary AE and SAE) and acute AE (peroral egg infection, primary AE and PAE). To assess the parasite proliferation potential, we measured parasite mass weight for SAE and liver lesion number for PAE. In both models, the parasite load was significantly decreased in response to anti-PD-L1 antibody treatment. In SAE, anti-PDL1 administration was associated with increased Th1 response parameters and decreased Treg responses, while in PAE anti-PDL1 administration was associated with fewer lesions in the liver and decreased Treg/Th2 responses. Our findings highly suggested that a PD-1/PD-L1 pathway blockade triggered the host immune responses in favour of an immune-mediated control of E. multilocularis proliferation. Based on this, future studies that combine PD-1/PD-L1 blockade with a parasitostatic albendazole medication may yield in a putatively curative therapeutic approach to control alveolar echinococcosis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology

UniBE Contributor:

Wang, Junhua; Jebbawi, Fadi; Beldi, Guido and Gottstein, Bruno

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0141-9838

Publisher:

Blackwell Scientific Publications

Language:

English

Submitter:

Bruno Gottstein

Date Deposited:

18 Dec 2018 13:24

Last Modified:

07 Feb 2019 05:36

Publisher DOI:

10.1111/pim.12596

PubMed ID:

30315719

Uncontrolled Keywords:

Echinococcus multilocularis PD-1 PD-L1 anti-PD-L1 immunotherapy

BORIS DOI:

10.7892/boris.122741

URI:

https://boris.unibe.ch/id/eprint/122741

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