Anti-PD-L1 Immunotherapy of Chronic Virus Infection Improves Virus Control without Augmenting Tissue Damage by Fibrosis.

Autor: Casella V; Infection Biology Laboratory, Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, 08003 Barcelona, Spain., Cebollada Rica P; Infection Biology Laboratory, Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, 08003 Barcelona, Spain., Argilaguet J; Institute of Agrifood Research and Technology (IRTA), Centre de Recerca en Sanitat Animal (CReSA), 08193 Barcelona, Spain.; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain.; WOAH Collaborating Centre for Emerging and Re-Emerging Pig Diseases in Europe, IRTA-CReSA, 08193 Barcelona, Spain., Vidal E; Institute of Agrifood Research and Technology (IRTA), Centre de Recerca en Sanitat Animal (CReSA), 08193 Barcelona, Spain.; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain.; WOAH Collaborating Centre for Emerging and Re-Emerging Pig Diseases in Europe, IRTA-CReSA, 08193 Barcelona, Spain., González-Cao M; Instituto Oncologico Dr. Rosell, Hospital Quiron-Dexeus Barcelona, 08028 Barcelona, Spain., Güerri-Fernandez R; Infectious Diseases Unit, Hospital del Mar, Institute of Medical Research (IMIM), 08003 Barcelona, Spain., Bocharov G; Marchuk Institute of Numerical Mathematics, Russian Academy of Sciences, 119991 Moscow, Russia.; Institute of Computer Science and Mathematical Modeling, Sechenov First Moscow State Medical University, 119635 Moscow, Russia., Meyerhans A; Infection Biology Laboratory, Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, 08003 Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2024 May 17; Vol. 16 (5). Date of Electronic Publication: 2024 May 17.
DOI: 10.3390/v16050799
Abstrakt: Immunotherapy with checkpoint inhibitors, albeit commonly used against tumors, is still at its infancy against chronic virus infections. It relies on the reinvigoration of exhausted T lymphocytes to eliminate virus-infected cells. Since T cell exhaustion is a physiological process to reduce immunopathology, the reinvigoration of these cells might be associated with an augmentation of pathological changes. To test this possibility, we here analyzed in the model system of chronic lymphocytic choriomeningitis virus (LCMV)-infected mice whether treatment with the checkpoint inhibitor anti-PD-L1 antibody would increase CD8 T cell-dependent fibrosis. We show that pre-existing spleen fibrosis did not worsen under conditions that increase CD8 T cell functionality and reduce virus loads suggesting that the CD8 T cell functionality increase remained below its pathogenicity threshold. These promising findings should further encourage immunotherapeutic trials against chronic virus infections.
Databáze: MEDLINE
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