{"doi":"10.1101/2023.03.05.531191","title":"Antigen-presenting type-I conventional dendritic cells facilitate curative checkpoint blockade immunotherapy in pancreatic cancer","abstract":"Abstract Inflammation and tissue damage associated with pancreatitis can precede or occur concurrently with pancreatic ductal adenocarcinoma (PDAC). We demonstrate that in PDAC coupled with pancreatitis (ptPDAC), antigen-presenting type-I conventional dendritic cells (cDC1s) are specifically activated. Immune checkpoint blockade therapy (iCBT) leads to cytotoxic CD8 + T cell activation and eradication of ptPDAC with restoration of lifespan even upon PDAC re-challenge. Such eradication of ptPDAC was reversed following specific depletion of dendritic cells. Employing PDAC antigen-loaded cDC1s as a vaccine, immunotherapy-resistant PDAC was rendered sensitive to iCBT with a curative outcome. Analysis of the T-cell receptor (TCR) sequences in the tumor infiltrating CD8 + T cells following cDC1 vaccination coupled with iCBT identified unique CDR3 sequences with potential therapeutic significance. Our findings identify a fundamental difference in the immune microenvironment and adaptive immune response in PDAC concurrent with, or without pancreatitis, and provides a rationale for combining cDC1 vaccination with iCBT as a potential treatment option.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":394273,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":515963,"name":"Allison M. Dyevoich","orcid":"0000-0002-4106-0435","position":1,"is_corresponding":false},{"id":1004387,"name":"Yang Chen","orcid":"0000-0001-6993-4870","position":2,"is_corresponding":false},{"id":662987,"name":"Bingrui Li","orcid":"0000-0002-4807-1452","position":3,"is_corresponding":false},{"id":235973,"name":"Hikaru Sugimoto","orcid":"0000-0003-0499-3962","position":4,"is_corresponding":false},{"id":1168606,"name":"Amari M. Sockwell","orcid":"0009-0008-1963-4181","position":5,"is_corresponding":false},{"id":235975,"name":"Kathleen M. McAndrews","orcid":"0000-0002-4092-4991","position":6,"is_corresponding":false},{"id":237056,"name":"Huamin Wang","orcid":"0000-0002-2038-5863","position":7,"is_corresponding":false},{"id":233455,"name":"Shabnam Shalapour","orcid":"0000-0002-4743-3706","position":8,"is_corresponding":false},{"id":277293,"name":"Stephanie S. Watowich","orcid":"0000-0003-1969-659X","position":9,"is_corresponding":false},{"id":104298,"name":"Raghu Kalluri","orcid":"0000-0002-2190-547X","position":10,"is_corresponding":false},{"id":920682,"name":"Krishnan K. Mahadevan","orcid":"0000-0002-6503-6851","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:19:10.334330Z","pmid":"36945457","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":[]}