{"doi":"10.7554/elife.52668","title":"Anti-PD-1 immunotherapy leads to tuberculosis reactivation via dysregulation of TNF-α","abstract":"Previously, we developed a 3-dimensional cell culture model of human tuberculosis (TB) and demonstrated its potential to interrogate the host-pathogen interaction (Tezera et al., 2017a). Here, we use the model to investigate mechanisms whereby immune checkpoint therapy for cancer paradoxically activates TB infection. In patients, PD-1 is expressed in Mycobacterium tuberculosis (Mtb)-infected lung tissue but is absent in areas of immunopathology. In the microsphere model, PD-1 ligands are up-regulated by infection, and the PD-1/PD-L1 axis is further induced by hypoxia. Inhibition of PD-1 signalling increases Mtb growth, and augments cytokine secretion. TNF-α is responsible for accelerated Mtb growth, and TNF-α neutralisation reverses augmented Mtb growth caused by anti-PD-1 treatment. In human TB, pulmonary TNF-α immunoreactivity is increased and circulating PD-1 expression negatively correlates with sputum TNF-α concentrations. Together, our findings demonstrate that PD-1 regulates the immune response in TB, and inhibition of PD-1 accelerates Mtb growth via excessive TNF-α secretion.","journal":"eLife","year":2020,"id":52601,"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":130,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"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":266673,"name":"Magdalena K. Bielecka","orcid":"0000-0002-1819-2552","position":1,"is_corresponding":false},{"id":266674,"name":"Paul Ogongo","orcid":"0000-0002-0093-5768","position":2,"is_corresponding":false},{"id":266675,"name":"Naomi F. Walker","orcid":"0000-0002-3345-7694","position":3,"is_corresponding":false},{"id":266676,"name":"Matthew J. Ellis","orcid":"0000-0002-5264-0531","position":4,"is_corresponding":false},{"id":266677,"name":"Diana J. Garay‐Baquero","orcid":"0000-0002-9450-8504","position":5,"is_corresponding":false},{"id":269149,"name":"Kristian Thomas","orcid":null,"position":6,"is_corresponding":false},{"id":266678,"name":"Michaela T. Reichmann","orcid":"0000-0002-6714-8400","position":7,"is_corresponding":false},{"id":266679,"name":"David A. Johnston","orcid":"0000-0001-6703-6014","position":8,"is_corresponding":false},{"id":266680,"name":"Katalin A. Wilkinson","orcid":"0000-0002-9796-2040","position":9,"is_corresponding":false},{"id":266681,"name":"Mohamed I. M. Ahmed","orcid":"0000-0003-4868-9380","position":10,"is_corresponding":false},{"id":269150,"name":"Sanjay Jogai","orcid":null,"position":11,"is_corresponding":false},{"id":266682,"name":"Suwan N. Jayasinghe","orcid":"0000-0002-7125-2219","position":12,"is_corresponding":false},{"id":266683,"name":"Robert J. Wilkinson","orcid":"0000-0002-2753-1800","position":13,"is_corresponding":false},{"id":266684,"name":"Salah Mansour","orcid":"0000-0002-5982-734X","position":14,"is_corresponding":false},{"id":247024,"name":"Gareth J. Thomas","orcid":"0000-0003-3832-7335","position":15,"is_corresponding":false},{"id":110384,"name":"Christian H. Ottensmeier","orcid":"0000-0003-3619-1657","position":16,"is_corresponding":false},{"id":104353,"name":"Alasdair Leslie","orcid":"0000-0003-2538-6467","position":17,"is_corresponding":false},{"id":266685,"name":"Paul Elkington","orcid":"0000-0003-0390-0613","position":18,"is_corresponding":false},{"id":266672,"name":"Liku B. Tezera","orcid":"0000-0002-7898-6709","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-18T20:43:25.742124Z","pmid":"32091388","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":[]}