{"doi":"10.1101/2022.05.24.493132","title":"Single-Cell RNA Sequencing Reveals the Effects of Chemotherapy on Human Pancreatic Adenocarcinoma and its Tumor Microenvironment","abstract":"Abstract The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) is a complex ecosystem that drives tumor progression; however, in-depth single cell characterization of the PDAC TME and its role in response to therapy is lacking. We performed single-cell RNA sequencing on freshly collected human PDAC samples either before or after chemotherapy. Overall, we found a heterogeneous mixture of basal and classical cancer cell subtypes, along with distinct cancer-associated fibroblast and macrophage subpopulations. Strikingly, classical and basal-like cancer cells exhibited similar transcriptional responses to chemotherapy, and did not demonstrate a shift towards a basal-like transcriptional program among treated samples. We observed decreased ligand-receptor interactions in treated samples, particularly TIGIT on CD8+ T cells and its receptor on cancer cells, and identified TIGIT as the major inhibitory checkpoint molecule of CD8+ T cells. Our results suggest that chemotherapy profoundly impacts the PDAC TME and may promote resistance to immunotherapy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":296816,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8896,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":984849,"name":"Daniel Weissinger","orcid":null,"position":1,"is_corresponding":false},{"id":2214,"name":"Emily Kawaler","orcid":"0000-0002-7438-7282","position":2,"is_corresponding":false},{"id":984139,"name":"Ende Zhao","orcid":"0000-0002-1355-6919","position":3,"is_corresponding":false},{"id":984140,"name":"Despoina Kalfakakou","orcid":"0000-0002-3369-2360","position":4,"is_corresponding":false},{"id":984850,"name":"Surajit Dhara","orcid":null,"position":5,"is_corresponding":false},{"id":984851,"name":"Grace Oh","orcid":null,"position":6,"is_corresponding":false},{"id":500437,"name":"Xiaohong Jing","orcid":null,"position":7,"is_corresponding":false},{"id":984852,"name":"Nina Beri","orcid":null,"position":8,"is_corresponding":false},{"id":984141,"name":"Lauren Khanna","orcid":"0000-0002-2445-9911","position":9,"is_corresponding":false},{"id":302057,"name":"Tamas A. Gonda","orcid":"0000-0002-0093-3738","position":10,"is_corresponding":false},{"id":347518,"name":"Paul E. Oberstein","orcid":"0000-0001-5918-6004","position":11,"is_corresponding":false},{"id":644954,"name":"Cristina Hajdu","orcid":"0000-0002-2856-9966","position":12,"is_corresponding":false},{"id":75654,"name":"Cynthia A. Loomis","orcid":"0000-0001-8668-1270","position":13,"is_corresponding":false},{"id":49812,"name":"Adriana Heguy","orcid":"0000-0002-2836-6683","position":14,"is_corresponding":false},{"id":103974,"name":"Mara H. Sherman","orcid":"0000-0001-7826-3888","position":15,"is_corresponding":false},{"id":516590,"name":"Amanda W. Lund","orcid":"0000-0001-7389-9983","position":16,"is_corresponding":false},{"id":984853,"name":"Theodore H. Welling","orcid":null,"position":17,"is_corresponding":false},{"id":238065,"name":"Igor Dolgalev","orcid":"0000-0003-4451-126X","position":18,"is_corresponding":false},{"id":69214,"name":"Aristotelis Tsirigos","orcid":"0000-0002-7512-8477","position":19,"is_corresponding":false},{"id":106458,"name":"Diane M. Simeone","orcid":"0000-0001-5142-3087","position":20,"is_corresponding":false},{"id":259271,"name":"Gregor Werba","orcid":"0000-0003-1464-9065","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:21.257700Z","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":[]}