{"doi":"10.1016/j.celrep.2023.112732","title":"Tumor-specific CD4 T cells instruct monocyte fate in pancreatic ductal adenocarcinoma","abstract":"Pancreatic ductal adenocarcinoma (PDA) orchestrates a suppressive tumor microenvironment that fosters immunotherapy resistance. Tumor-associated macrophages (TAMs) are the principal immune cell infiltrating PDA and are heterogeneous. Here, by employing macrophage fate-mapping approaches and single-cell RNA sequencing, we show that monocytes give rise to most macrophage subsets in PDA. Tumor-specific CD4, but not CD8, T cells promote monocyte differentiation into MHCII hi anti-tumor macrophages. By conditional major histocompatibility complex (MHC) class II deletion on monocyte-derived macrophages, we show that tumor antigen presentation is required for instructing monocyte differentiation into anti-tumor macrophages, promoting Th1 cells, abrogating Treg cells, and mitigating CD8 T cell exhaustion. Non-redundant IFNγ and CD40 promote MHCII hi anti-tumor macrophages. Intratumoral monocytes adopt a pro-tumor fate indistinguishable from that of tissue-resident macrophages following loss of macrophage MHC class II or tumor-specific CD4 T cells. Thus, tumor antigen presentation by macrophages to CD4 T cells dictates TAM fate and is a major determinant of macrophage heterogeneity in cancer.","journal":"Cell Reports","year":2023,"id":319773,"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":53,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"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":445732,"name":"Adam L. Burrack","orcid":"0000-0002-4001-7849","position":1,"is_corresponding":false},{"id":864642,"name":"Yingzheng Xu","orcid":"0009-0004-9197-1300","position":2,"is_corresponding":false},{"id":1016649,"name":"Grant H. Hickok","orcid":"0009-0004-8235-4773","position":3,"is_corresponding":false},{"id":658616,"name":"Zoe C. Schmiechen","orcid":"0000-0002-3403-6824","position":4,"is_corresponding":false},{"id":627090,"name":"Samuel Becker","orcid":null,"position":5,"is_corresponding":false},{"id":920831,"name":"Eduardo Cruz-Hinojoza","orcid":"0000-0003-3279-133X","position":6,"is_corresponding":false},{"id":247524,"name":"Patricia R. Schrank","orcid":"0000-0001-5095-7896","position":7,"is_corresponding":false},{"id":1011280,"name":"Ainsley E. Kennedy","orcid":null,"position":8,"is_corresponding":false},{"id":678986,"name":"Maria Firulyova","orcid":"0000-0002-4839-5115","position":9,"is_corresponding":false},{"id":907777,"name":"Ebony A. Miller","orcid":null,"position":10,"is_corresponding":false},{"id":247521,"name":"Konstantin Zaitsev","orcid":"0000-0003-3749-0886","position":11,"is_corresponding":false},{"id":230325,"name":"Jesse W. Williams","orcid":"0000-0003-3815-0891","position":12,"is_corresponding":false},{"id":513391,"name":"Ingunn M. Stromnes","orcid":"0000-0001-8120-4547","position":13,"is_corresponding":false},{"id":907328,"name":"Michael T. Patterson","orcid":"0000-0002-7632-7267","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-19T01:07:17.361058Z","pmid":"37402168","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":[]}