Publikationsdatenbank

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 (2020)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

David, Paul

Drabczyk-Pluta, Malgorzata

Pastille, Eva

Knuschke, Torben

Werner, Tanja

Honke, Nadine

Megger, Dominik A.

Akhmetzyanova, Ilseyar

Shaabani, Namir

Eyking-Singer, Annette

Cario, Elke

Kershaw, Olivia (WE 12)

Gruber, Achim D. (WE 12)

Tenbusch, Matthias

Dietze, Kirsten K.

Trilling, Mirko

Liu, Jia

Schadendorf, Dirk

Streeck, Hendrik

Lang, Karl S.

Xie, Youhua

Zimmer, Lisa

Sitek, Barbara

Paschen, Annette

Westendorf, Astrid M.

Dittmer, Ulf

Zelinskyy, Gennadiy

Quelle

PLoS pathogens

Bandzählung: 16

Heftzählung: 3

Seiten: e1008340

ISSN: 1553-7374

Sprache

Englisch

Verweise

URL (Volltext): https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008340

DOI: 10.1371/journal.ppat.1008340

Pubmed: 32226027

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.