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Merck
  • Combination immunotherapy with anti-PD-L1 antibody and depletion of regulatory T cells during acute viral infections results in improved virus control but lethal immunopathology.

Combination immunotherapy with anti-PD-L1 antibody and depletion of regulatory T cells during acute viral infections results in improved virus control but lethal immunopathology.

PLoS pathogens (2020-04-01)
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
摘要

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.

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β-丙内酯, Grade II, ≥90%