{"doi":"10.1136/jitc-2019-000244","title":"NF-κB p50-deficient immature myeloid cell (p50-IMC) adoptive transfer slows the growth of murine prostate and pancreatic ductal carcinoma","abstract":"Background Macrophages and dendritic cells lacking the transcription factor nuclear factor kappa B p50 are skewed toward a proinflammatory phenotype, with increased cytokine expression and enhanced T cell activation; additionally, murine melanoma, fibrosarcoma, colon carcinoma, and glioblastoma grow slower in p50 −/ − mice. We therefore evaluated the efficacy of p50-negative immature myeloid cells (p50-IMCs) adoptively transferred into tumor-bearing hosts. Immature cells were used to maximize tumor localization, and pretreatment with 5-fluorouracil (5FU) was examined due to its potential to impair marrow production of myeloid cells, to target tumor myeloid cells and to release tumor neoantigens. Methods Wild-type (WT)-IMC or p50-IMC were generated by culturing lineage-negative marrow cells from WT or p50 −/ − mice in media containing thrombopoietin, stem cell factor and Flt3 ligand for 6 days followed by monocyte colony-stimulating factor for 1 day on ultralow attachment plates. Mice inoculated with Hi-Myc prostate cancer (PCa) cells or K-Ras G12D pancreatic ductal carcinoma (PDC)-luciferase cells received 5FU followed 5 days later by three doses of 10 7 immature myeloid cells (IMC) every 3–4 days. Results PCa cells grew slower in p50 −/ − mice, and absence of host p50 prolonged the survival of mice inoculated orthotopically with PDC cells. IMC from Cytomegalovirus (CMV)-luciferase mice localized to tumor, nodes, spleen, marrow, and lung. 5FU followed by p50-IMC slowed PCa and PDC tumor growth, ~3-fold on average, in contrast to 5FU followed by WT-IMC, 5FU alone or p50-IMC alone. Slowed tumor growth was evident for 93% of PCa but only 53% of PDC tumors; we therefore focused on PCa for additional IMC analyses. In PCa, p50-IMC matured into F4/80 + macrophages, as well as CD11b + F4/80 − CD11c + conventional dendritic cells (cDCs). In both tumor and draining lymph nodes, p50-IMC generated more macrophages and cDCs than WT-IMC. Activated tumor CD8 + T cells were increased fivefold by p50-IMC compared with WT-IMC, and antibody-mediated CD8 + T cell depletion obviated slower tumor growth induced by 5FU followed by p50-IMC. Conclusions 5FU followed by p50-IMC slows the growth of murine prostate and pancreatic carcinoma and depends on CD8 + T cell activation. Deletion of p50 in patient-derived marrow CD34 + cells and subsequent production of IMC for adoptive transfer may contribute to the therapy of these and additional cancers.","journal":"Journal for ImmunoTherapy of Cancer","year":2020,"id":81728,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"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":422322,"name":"David J. Barakat","orcid":"0000-0001-7057-178X","position":1,"is_corresponding":false},{"id":422323,"name":"Theresa J. Barberi","orcid":"0000-0002-7816-1969","position":2,"is_corresponding":false},{"id":422324,"name":"Lei Zheng","orcid":"0000-0002-8342-5236","position":3,"is_corresponding":false},{"id":7890,"name":"Elizabeth M. Jaffee","orcid":"0000-0003-3841-6549","position":4,"is_corresponding":false},{"id":64727,"name":"Kenneth J. Pienta","orcid":"0000-0002-4138-2186","position":5,"is_corresponding":false},{"id":422325,"name":"Alan D. Friedman","orcid":"0000-0002-5615-7061","position":6,"is_corresponding":false},{"id":422321,"name":"Rahul Suresh","orcid":"0000-0002-0805-261X","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:52:58.921847Z","pmid":"31940589","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":[]}