{"doi":"10.1016/j.celrep.2024.114819","title":"PD-L1 restrains PD-1+Nrp1lo Treg cells to suppress inflammation-driven colorectal tumorigenesis","abstract":"T cells function not only as an essential component of host cancer immunosurveillance but also as a regulator of colonic inflammation, a process that promotes colorectal cancer. Programmed death-ligand 1 (PD-L1) is a T cell-negative regulator, but its role in regulation of T cell functions in the context of colorectal cancer is unknown. We report that global deletion of Cd274 results in increased colonic inflammation, PD-1 + T cells, and inflammation-driven colorectal tumorigenesis in mice. Single-cell RNA sequencing (scRNA-seq) analysis revealed that PD-L1 suppresses subpopulations of programmed cell death protein 1 (PD-1) + Nrp1 lo regulatory T (Treg) cells and interleukin (IL) 6 + neutrophils in colorectal tumor. Treg cells produce transforming growth factor (TGF) β to recruit IL6 + neutrophils. Neutrophils produce IL6 to inhibit activation of tumor-specific cytotoxic T lymphocytes (CTLs) and primary CTLs. Accordingly, IL6 blockade immunotherapy increases CTL activation and suppresses colon tumor growth in vivo . Our findings determine that PD-L1 restrains PD-1 + Nrp1 lo TGFβ + Treg cells to suppress IL6 + neutrophil tumor recruitment to sustain CTL activation to control inflammation-driven colorectal tumorigenesis.","journal":"Cell Reports","year":2024,"id":454961,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.948,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":257442,"name":"John D. Klement","orcid":"0000-0003-4334-4076","position":1,"is_corresponding":false},{"id":661913,"name":"Alyssa D. Merting","orcid":"0000-0001-9911-5905","position":2,"is_corresponding":false},{"id":257443,"name":"Chunwan Lu","orcid":"0000-0002-3823-9434","position":3,"is_corresponding":false},{"id":659593,"name":"Yang Zhao","orcid":"0000-0002-1362-9823","position":4,"is_corresponding":false},{"id":263717,"name":"Dafeng Yang","orcid":"0000-0002-8320-8215","position":5,"is_corresponding":false},{"id":1036254,"name":"Wei Xiao","orcid":"0000-0002-8426-9060","position":6,"is_corresponding":false},{"id":632392,"name":"Huabin Zhu","orcid":"0000-0002-4557-795X","position":7,"is_corresponding":false},{"id":1278790,"name":"Ponnala Rajeshwari","orcid":null,"position":8,"is_corresponding":false},{"id":1278408,"name":"Michael Toscano","orcid":"0000-0002-1772-6479","position":9,"is_corresponding":false},{"id":900679,"name":"Kimya Jones","orcid":"0000-0001-8313-1695","position":10,"is_corresponding":false},{"id":943408,"name":"Amanda Barrett","orcid":"0009-0006-0135-9033","position":11,"is_corresponding":false},{"id":249679,"name":"Roni J. Bollag","orcid":"0000-0003-4963-6619","position":12,"is_corresponding":false},{"id":849628,"name":"Padraic G. Fallon","orcid":"0000-0002-8401-7293","position":13,"is_corresponding":false},{"id":249681,"name":"Huidong Shi","orcid":"0000-0003-1137-3390","position":14,"is_corresponding":false},{"id":257444,"name":"Kebin Liu","orcid":"0000-0003-1965-7240","position":15,"is_corresponding":false},{"id":260830,"name":"Dakota B. Poschel","orcid":null,"position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:03:12.720997Z","pmid":"39368087","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":[]}