{"doi":"10.1172/jci.insight.144394","title":"PDLIM2 repression by ROS in alveolar macrophages promotes lung tumorigenesis","abstract":"One of the most fundamental and challenging questions in the field of cancer is how immunity is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identified the tumor suppressor PDZ-LIM domain-containing protein 2 (PDLIM2) as a checkpoint of alveolar macrophages (AMs) important for lung tumor suppression. During lung tumorigenesis, PDLIM2 expression in AMs is downregulated by ROS-activated transcription repressor BTB and CNC homology 1 (BACH1). PDLIM2 downregulation leads to constitutive activation of the transcription factor STAT3, driving AM protumorigenic polarization/activation and differentiation from monocytes attracted from the circulation to suppress cytotoxic T lymphocytes and promote lung cancer. PDLIM2 downregulation also decreases AM phagocytosis. These findings establish ROS/BACH1/PDLIM2/STAT3 as a signaling pathway driving AMs for lung tumor promotion.","journal":"JCI Insight","year":2021,"id":162828,"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":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9611,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":680643,"name":"Fan Sun","orcid":"0000-0002-4669-121X","position":1,"is_corresponding":false},{"id":680644,"name":"Lei Han","orcid":"0000-0001-9088-2403","position":2,"is_corresponding":false},{"id":362146,"name":"Xujie Liu","orcid":"0000-0001-8713-4287","position":3,"is_corresponding":false},{"id":681274,"name":"Yadong Xiao","orcid":null,"position":4,"is_corresponding":false},{"id":306818,"name":"Alyssa D. Gregory","orcid":"0000-0002-0392-7202","position":5,"is_corresponding":false},{"id":306819,"name":"Steven D. Shapiro","orcid":"0000-0002-7137-1322","position":6,"is_corresponding":false},{"id":309440,"name":"Gutian Xiao","orcid":null,"position":7,"is_corresponding":false},{"id":306820,"name":"Zhaoxia Qu","orcid":"0000-0002-2769-9814","position":8,"is_corresponding":false},{"id":680642,"name":"Liwen Li","orcid":"0000-0003-3726-5013","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:45:05.641178Z","pmid":"33539325","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":[]}