{"doi":"10.1101/2022.06.21.497084","title":"Arginase 1 is a key driver of immune suppression in pancreatic cancer","abstract":"Abstract An extensive fibroinflammatory stroma rich in macrophages is a hallmark of pancreatic cancer. In this disease, it is well appreciated that macrophages are immunosuppressive and contribute to the poor response to immunotherapy; however, the mechanisms of immune suppression are complex and not fully understood. Immunosuppressive macrophages are classically defined by expression of the enzyme Arginase 1 (Arg1), which we demonstrated is potently expressed in pancreatic tumor associated macrophages from both human patients and mouse models. While routinely used as a polarization marker, Arg1 also catabolizes arginine, an amino acid required for T cell activation and proliferation. To investigate this metabolic function, we used a genetic and a pharmacologic approach to target Arg1 in pancreatic cancer. Genetic inactivation of Arg1 in macrophages, using a dual recombinase genetically engineered mouse model of pancreatic cancer, delayed formation of invasive disease, while increasing CD8 + T cell infiltration. Treatment of established tumors with the arginase inhibitor CB-1158 exhibited further increased CD8 + T cell infiltration, beyond that seen with the macrophage-specific knockout, and sensitized the tumors to anti-PD1 immune checkpoint blockade. Thus, our data demonstrate that Arg1 is more than simply a marker of macrophage function. Rather, Arg1 is also a driver of immune suppression and represents a promising immunotherapeutic target for pancreatic cancer.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297737,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"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":225034,"name":"Zeribe C. Nwosu","orcid":"0000-0003-1641-2045","position":1,"is_corresponding":false},{"id":564797,"name":"Wenting Du","orcid":"0000-0001-6765-0129","position":2,"is_corresponding":false},{"id":225414,"name":"Katelyn L. Donahue","orcid":"0000-0001-9535-9275","position":3,"is_corresponding":false},{"id":225400,"name":"Carlos E. Espinoza","orcid":"0009-0000-0460-1514","position":4,"is_corresponding":false},{"id":620173,"name":"Kristee Brown","orcid":"0000-0002-5123-4945","position":5,"is_corresponding":false},{"id":623505,"name":"Ashley Velez-Delgado","orcid":"0000-0002-1506-9305","position":6,"is_corresponding":false},{"id":453452,"name":"Wei Yan","orcid":"0000-0003-1535-3100","position":7,"is_corresponding":false},{"id":225403,"name":"Fatima Lima","orcid":"0000-0003-1384-6040","position":8,"is_corresponding":false},{"id":986271,"name":"Allison C. Bischoff","orcid":"0000-0001-5119-5272","position":9,"is_corresponding":false},{"id":236214,"name":"Padma Kadiyala","orcid":"0000-0002-3273-9905","position":10,"is_corresponding":false},{"id":476729,"name":"Daniel James Salas-Escabillas","orcid":"0000-0002-0819-989X","position":11,"is_corresponding":false},{"id":225419,"name":"Howard C. Crawford","orcid":"0000-0001-9360-3019","position":12,"is_corresponding":false},{"id":225420,"name":"Filip Bednar","orcid":"0000-0001-5193-9817","position":13,"is_corresponding":false},{"id":225393,"name":"Eileen S. Carpenter","orcid":"0000-0001-6775-6943","position":14,"is_corresponding":false},{"id":463891,"name":"Yaqing Zhang","orcid":"0009-0000-6019-0844","position":15,"is_corresponding":false},{"id":238042,"name":"Christopher J. Halbrook","orcid":"0000-0002-3376-3114","position":16,"is_corresponding":false},{"id":106351,"name":"Costas A. Lyssiotis","orcid":"0000-0001-9309-6141","position":17,"is_corresponding":false},{"id":225422,"name":"Marina Pasca di Magliano","orcid":"0000-0001-9632-9035","position":18,"is_corresponding":false},{"id":623506,"name":"Rosa E. Menjivar","orcid":"0000-0003-1551-869X","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T00:31:31.270564Z","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":[]}