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

David P, Drabczyk-Pluta M, Pastille E, Knuschke T, Werner T, Honke N, Megger DA, Akhmetzyanova I, Shaabani N, Eyking-Singer A, Cario E, Kershaw O, Gruber AD, Tenbusch M, Dietze KK, Trilling M, Liu J, Schadendorf D, Streeck H, Lang KS, Xie Y, Zimmer L, Sitek B, Paschen A, Westendorf AM, Dittmer U, Zelinskyy G (2020)

Publication Type: Journal article

Publication year: 2020

Journal

PLoS Pathogens Public Library of Science

Book Volume: 16

Pages Range: e1008340-

Journal Issue: 3

DOI: 10.1371/journal.ppat.1008340

Abstract

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.

Authors with CRIS profile

Matthias Tenbusch Professur für Genbasierte Immunisierungsverfahren

Involved external institutions

Universitätsklinikum Essen DE Germany (DE) Universitätsklinikum Düsseldorf DE Germany (DE) Ruhr-Universität Bochum (RUB) DE Germany (DE) Freie Universität Berlin DE Germany (DE) Huazhong University of Science & Technology CN China (CN) Fudan University / 复旦大学 CN China (CN)

How to cite

APA:

David, P., Drabczyk-Pluta, M., Pastille, E., Knuschke, T., Werner, T., Honke, N.,... Zelinskyy, G. (2020). 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, 16(3), e1008340-. https://doi.org/10.1371/journal.ppat.1008340

MLA:

David, Paul, et al. "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 16.3 (2020): e1008340-.

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