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Parasite Immunol. 2018 Dec;40(12):e12596. doi: 10.1111/pim.12596. Epub 2018 Nov 4.

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

Author information

1
Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, Institute of Parasitology, University of Bern, Bern, Switzerland.
2
Department of Visceral Surgery and Medicine, Inselspital, University Hospital of Bern, Bern, Switzerland.
3
Chrono-Environment UMR/CNRS 6249, University of Bourgogne Franche-Comté, Besançon, France.
4
Parasitology Mycology Department, University Hospital Jean Minjoz, Besancon, France.

Abstract

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.

KEYWORDS:

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

PMID:
30315719
PMCID:
PMC6587932
DOI:
10.1111/pim.12596
[Indexed for MEDLINE]
Free PMC Article

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