{"doi":"10.1101/2021.06.18.449028","title":"Tumor PD-L1 selectively suppresses type I interferon in myeloid cells to suppress CTL recruitment to promote lung metastasis","abstract":"Abstract The mechanism underlying tumor cell PD-L1 (tPD-L1) induction of immune suppression through T cell PD-1 is well-known, but the mechanism underlying tPD-L1 induction of immune suppression via an intermediate cell is incompletely understood. We report here that tPD-L1 does not suppress cytotoxic T lymphocyte (CTL) activation and lytic function when only tumor cells and CTLs are present. Strikingly, knocking out PD-L1 in tumor cells has no effect on primary tumor growth, but significantly decreases lung metastasis in a CTL-dependent manner. Depletion of myeloid cells impaired tPD-L1 promotion of lung metastasis. Single-cell RNA sequencing revealed that tPD-L1 engages myeloid PD-1 (mPD-1) to antagonize type I interferon (IFN-I) and STAT1 signaling to repress Cxcl9 and Cxcl10 expression to impair CTL recruitment to lung metastases. Human patient response to PD-1 blockade immunotherapy correlates with IFN-I response in myeloid cells. Our data determines that the tPD-L1/mPD-1/IFN-I/STAT1/Cxcl9/10 axis controls CTL tumor infiltration in lung metastasis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":225481,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"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":260831,"name":"Priscilla S. Redd","orcid":null,"position":1,"is_corresponding":false},{"id":325167,"name":"Chunwan Lu","orcid":"0000-0001-6458-8462","position":2,"is_corresponding":false},{"id":661913,"name":"Alyssa D. Merting","orcid":"0000-0001-9911-5905","position":3,"is_corresponding":false},{"id":260830,"name":"Dakota B. Poschel","orcid":null,"position":4,"is_corresponding":false},{"id":263717,"name":"Dafeng Yang","orcid":"0000-0002-8320-8215","position":5,"is_corresponding":false},{"id":311562,"name":"Gang Zhou","orcid":"0000-0001-8967-114X","position":6,"is_corresponding":false},{"id":242939,"name":"David H. Munn","orcid":"0000-0002-7711-2858","position":7,"is_corresponding":false},{"id":257444,"name":"Kebin Liu","orcid":"0000-0003-1965-7240","position":8,"is_corresponding":false},{"id":257442,"name":"John D. Klement","orcid":"0000-0003-4334-4076","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-18T23:54:26.581453Z","pmid":null,"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":[]}