{"doi":"10.1126/science.abb3420","title":"p21 produces a bioactive secretome that places stressed cells under immunosurveillance","abstract":"Immune cells identify and destroy damaged cells to prevent them from causing cancer or other pathologies by mechanisms that remain poorly understood. Here, we report that the cell-cycle inhibitor p21 places cells under immunosurveillance to establish a biological timer mechanism that controls cell fate. p21 activates retinoblastoma protein (Rb)–dependent transcription at select gene promoters to generate a complex bioactive secretome, termed p21-activated secretory phenotype (PASP). The PASP includes the chemokine CXCL14, which promptly attracts macrophages. These macrophages disengage if cells normalize p21 within 4 days, but if p21 induction persists, they polarize toward an M1 phenotype and lymphocytes mount a cytotoxic T cell response to eliminate target cells, including preneoplastic cells. Thus, p21 concurrently induces proliferative arrest and immunosurveillance of cells under duress.","journal":"Science","year":2021,"id":146015,"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":274,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"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":280869,"name":"Cheng Zhang","orcid":"0000-0003-3843-1562","position":1,"is_corresponding":false},{"id":620399,"name":"Chance Sine","orcid":"0000-0002-7184-146X","position":2,"is_corresponding":false},{"id":622139,"name":"Erik-Jan van Deursen","orcid":null,"position":3,"is_corresponding":false},{"id":384811,"name":"Karthik B. Jeganathan","orcid":"0000-0001-5587-1266","position":4,"is_corresponding":false},{"id":622140,"name":"Naomi Hamada","orcid":null,"position":5,"is_corresponding":false},{"id":620400,"name":"Jan Grašič","orcid":"0000-0002-0534-9565","position":6,"is_corresponding":false},{"id":620401,"name":"David J. Friedman","orcid":"0000-0002-1295-1562","position":7,"is_corresponding":false},{"id":622141,"name":"Jeremy Stutchman","orcid":null,"position":8,"is_corresponding":false},{"id":620402,"name":"İsmail Can","orcid":"0000-0003-0569-5326","position":9,"is_corresponding":false},{"id":622142,"name":"Masakazu Hamada","orcid":null,"position":10,"is_corresponding":false},{"id":620403,"name":"Do Young Lim","orcid":"0000-0002-7663-5905","position":11,"is_corresponding":false},{"id":70826,"name":"Jeong‐Heon Lee","orcid":"0000-0003-4007-9166","position":12,"is_corresponding":false},{"id":70829,"name":"Tamás Ördög","orcid":"0000-0002-3940-7284","position":13,"is_corresponding":false},{"id":229147,"name":"Rémi-Martin Laberge","orcid":"0000-0002-5841-5781","position":14,"is_corresponding":false},{"id":404865,"name":"Virginia Smith Shapiro","orcid":"0000-0001-9978-341X","position":15,"is_corresponding":false},{"id":277286,"name":"Darren J. Baker","orcid":"0000-0001-9006-1939","position":16,"is_corresponding":false},{"id":31912,"name":"Hu Li","orcid":"0000-0001-5957-5472","position":17,"is_corresponding":false},{"id":384817,"name":"Jan M. van Deursen","orcid":"0000-0002-3042-5267","position":18,"is_corresponding":false},{"id":384812,"name":"Ines Sturmlechner","orcid":"0000-0003-1272-5618","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-18T23:42:18.947086Z","pmid":"34709885","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":[]}