{"doi":"10.1371/journal.ppat.1008340","title":"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","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.","journal":"PLoS Pathogens","year":2020,"id":81022,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":421045,"name":"Malgorzata Drabczyk-Pluta","orcid":null,"position":1,"is_corresponding":false},{"id":421046,"name":"Eva Pastille","orcid":null,"position":2,"is_corresponding":false},{"id":419667,"name":"Torben Knuschke","orcid":"0000-0002-2273-1475","position":3,"is_corresponding":false},{"id":421047,"name":"Tanja Werner","orcid":null,"position":4,"is_corresponding":false},{"id":419668,"name":"Nadine Honke","orcid":"0000-0002-2220-6806","position":5,"is_corresponding":false},{"id":419669,"name":"Dominik A. Megger","orcid":"0000-0002-1058-7744","position":6,"is_corresponding":false},{"id":310626,"name":"Ilseyar Akhmetzyanova","orcid":"0000-0002-4446-3475","position":7,"is_corresponding":false},{"id":419670,"name":"Namir Shaabani","orcid":"0000-0003-3548-5899","position":8,"is_corresponding":false},{"id":419671,"name":"Annette Eyking-Singer","orcid":"0000-0003-3003-2006","position":9,"is_corresponding":false},{"id":419672,"name":"Elke Cario","orcid":"0000-0003-2472-4495","position":10,"is_corresponding":false},{"id":419673,"name":"Olivia Kershaw","orcid":"0000-0002-3686-9993","position":11,"is_corresponding":false},{"id":230492,"name":"Achim D. Gruber","orcid":"0000-0002-4502-0393","position":12,"is_corresponding":false},{"id":419674,"name":"Matthias Tenbusch","orcid":"0000-0003-3951-9056","position":13,"is_corresponding":false},{"id":421048,"name":"Kirsten K. Dietze","orcid":null,"position":14,"is_corresponding":false},{"id":419675,"name":"Mirko Trilling","orcid":"0000-0003-3659-3541","position":15,"is_corresponding":false},{"id":419676,"name":"Jia Liu","orcid":"0000-0001-8424-7972","position":16,"is_corresponding":false},{"id":5602,"name":"Dirk Schadendorf","orcid":"0000-0003-3524-7858","position":17,"is_corresponding":false},{"id":64607,"name":"Hendrik Streeck","orcid":"0000-0002-0335-6390","position":18,"is_corresponding":false},{"id":351617,"name":"Karl S. Lang","orcid":"0000-0001-9783-7605","position":19,"is_corresponding":false},{"id":237957,"name":"Youhua Xie","orcid":"0000-0002-2416-7708","position":20,"is_corresponding":false},{"id":28947,"name":"Lisa Zimmer","orcid":"0000-0002-3680-3521","position":21,"is_corresponding":false},{"id":173218,"name":"Barbara Sitek","orcid":null,"position":22,"is_corresponding":false},{"id":28968,"name":"Annette Paschen","orcid":"0000-0003-1651-1262","position":23,"is_corresponding":false},{"id":419677,"name":"Astrid M. Westendorf","orcid":"0000-0002-2121-2892","position":24,"is_corresponding":false},{"id":419678,"name":"Ulf Dittmer","orcid":"0000-0001-9284-4849","position":25,"is_corresponding":false},{"id":419679,"name":"Gennadiy Zelinskyy","orcid":"0000-0001-6338-2382","position":26,"is_corresponding":false},{"id":419666,"name":"Paul David","orcid":"0000-0002-9643-3657","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-18T21:52:34.401799Z","pmid":"32226027","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}