Open AccessCombination immunotherapy with anti-PD-L1 antibody and depletion of regulatory T cells during acute viral infections results in improved virus control but lethal immunopathology
Author(s) -
Paul David,
Malgorzata Drabczyk-Pluta,
Eva Pastille,
Torben Knuschke,
Tanja Werner,
Nadine Honke,
Dominik A. Megger,
Ilseyar Akhmetzyanova,
Namir Shaabani,
Annette Eyking-Singer,
Elke Cario,
Olivia Kershaw,
Achim D. Gruber,
Matthias Tenbusch,
Kirsten K. Dietze,
Mirko Trilling,
Jia Liu,
Dirk Schadendorf,
Hendrik Streeck,
Karl S. Lang,
Youhua Xie,
Lisa Zimmer,
Barbara Sitek,
Annette Paschen,
Astrid M. Westendorf,
Ulf Dittmer,
Gennadiy Zelinskyy
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008340
Subject(s) - immunology , immunotherapy , immunopathology , granzyme b , immune system , granzyme , cd8 , cytotoxic t cell , virus , medicine , virology , biology , perforin , biochemistry , in vitro
Combination immunotherapy (CIT) is currently applied as a treatment for different cancers and is proposed as a cure strategy for chronic viral infections. Whether such therapies are efficient during an acute infection remains elusive. To address this, inhibitory receptors were blocked and regulatory T cells depleted in acutely Friend retrovirus-infected mice. CIT resulted in a dramatic expansion of cytotoxic CD4+ and CD8+ T cells and a subsequent reduction in viral loads. Despite limited viral replication, mice developed fatal immunopathology after CIT. The pathology was most severe in the gastrointestinal tract and was mediated by granzyme B producing CD4+ and CD8+ T cells. A similar post-CIT pathology during acute Influenza virus infection of mice was observed, which could be prevented by vaccination. Melanoma patients who developed immune-related adverse events under immune checkpoint CIT also presented with expanded granzyme-expressing CD4+ and CD8+ T cell populations. Our data suggest that acute infections may induce immunopathology in patients treated with CIT, and that effective measures for infection prevention should be applied.