{"doi":"10.1084/jem.20220503","title":"WNT signaling in the tumor microenvironment promotes immunosuppression in murine pancreatic cancer","abstract":"Pancreatic ductal adenocarcinoma (PDA) is associated with activation of WNT signaling. Whether this signaling pathway regulates the tumor microenvironment has remained unexplored. Through single-cell RNA sequencing of human pancreatic cancer, we discovered that tumor-infiltrating CD4+ T cells express TCF7, encoding for the transcription factor TCF1. We conditionally inactivated Tcf7 in CD4 expressing T cells in a mouse model of pancreatic cancer and observed changes in the tumor immune microenvironment, including more CD8+ T cells and fewer regulatory T cells, but also compensatory upregulation of PD-L1. We then used a clinically available inhibitor of Porcupine, a key component of WNT signaling, and observed similar reprogramming of the immune response. WNT signaling inhibition has limited therapeutic window due to toxicity, and PD-L1 blockade has been ineffective in PDA. Here, we show that combination targeting reduces pancreatic cancer growth in an experimental model and might benefit the treatment of pancreatic cancer.","journal":"The Journal of Experimental Medicine","year":2022,"id":237568,"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":60,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"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":623506,"name":"Rosa E. Menjivar","orcid":"0000-0003-1551-869X","position":1,"is_corresponding":false},{"id":225414,"name":"Katelyn L. Donahue","orcid":"0000-0001-9535-9275","position":2,"is_corresponding":false},{"id":236214,"name":"Padma Kadiyala","orcid":"0000-0002-3273-9905","position":3,"is_corresponding":false},{"id":623505,"name":"Ashley Velez-Delgado","orcid":"0000-0002-1506-9305","position":4,"is_corresponding":false},{"id":620173,"name":"Kristee Brown","orcid":"0000-0002-5123-4945","position":5,"is_corresponding":false},{"id":860255,"name":"Hannah R. Watkoske","orcid":"0000-0003-2518-6457","position":6,"is_corresponding":false},{"id":860256,"name":"Xi He","orcid":"0000-0002-5802-2507","position":7,"is_corresponding":false},{"id":225393,"name":"Eileen S. Carpenter","orcid":"0000-0001-6775-6943","position":8,"is_corresponding":false},{"id":242857,"name":"Christina V. Angeles","orcid":"0000-0002-6500-9589","position":9,"is_corresponding":false},{"id":860257,"name":"Yaqing Zhang","orcid":"0000-0002-9185-4364","position":10,"is_corresponding":false},{"id":225422,"name":"Marina Pasca di Magliano","orcid":"0000-0001-9632-9035","position":11,"is_corresponding":false},{"id":564797,"name":"Wenting Du","orcid":"0000-0001-6765-0129","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T00:22:21.693802Z","pmid":"36239683","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":[]}