{"doi":"10.7554/elife.96925.2","title":"Propionyl-CoA carboxylase subunit B regulates anti-tumor T cells in a pancreatic cancer mouse model","abstract":"Most human pancreatic ductal adenocarcinoma (PDAC) are not infiltrated with cytotoxic T cells and are highly resistant to immunotherapy. Over 90% of PDAC have oncogenic KRAS mutations, and phosphoinositide 3-kinases (PI3Ks) are direct effectors of KRAS. Our previous study demonstrated that ablation of Pik3ca in KPC ( Kras G12D ; Trp53 R172H ; Pdx1-Cre ) pancreatic cancer cells induced host T cells to infiltrate and completely eliminate the tumors in a syngeneic orthotopic implantation mouse model. Now, we show that implantation of Pik3ca −/− KPC (named αKO) cancer cells induces clonal enrichment of cytotoxic T cells infiltrating the pancreatic tumors. To identify potential molecules that can regulate the activity of these anti-tumor T cells, we conducted an in vivo genome-wide gene-deletion screen using αKO cells implanted in the mouse pancreas. The result shows that deletion of propionyl-CoA carboxylase subunit B gene ( Pccb ) in αKO cells (named p-αKO) leads to immune evasion, tumor progression, and death of host mice. Surprisingly, p-αKO tumors are still infiltrated with clonally enriched CD8 + T cells but they are inactive against tumor cells. However, blockade of PD-L1/PD1 interaction reactivated these clonally enriched T cells infiltrating p-αKO tumors, leading to slower tumor progression and improve survival of host mice. These results indicate that Pccb can modulate the activity of cytotoxic T cells infiltrating some pancreatic cancers and this understanding may lead to improvement in immunotherapy for this difficult-to-treat cancer.","journal":"eLife","year":2025,"id":562895,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1328993,"name":"Richard Efem","orcid":null,"position":1,"is_corresponding":false},{"id":405546,"name":"Barbara Rosati","orcid":null,"position":2,"is_corresponding":false},{"id":1328528,"name":"Kevin Lü","orcid":"0000-0002-2588-9059","position":3,"is_corresponding":false},{"id":587257,"name":"Sara Maimouni","orcid":"0000-0002-6085-0766","position":4,"is_corresponding":false},{"id":1256441,"name":"Yaping Jiang","orcid":"0000-0002-6614-0079","position":5,"is_corresponding":false},{"id":937446,"name":"Valeria Montoya","orcid":null,"position":6,"is_corresponding":false},{"id":1328994,"name":"A. van der Velden","orcid":null,"position":7,"is_corresponding":false},{"id":244936,"name":"Wei‐Xing Zong","orcid":"0000-0002-3129-8220","position":8,"is_corresponding":false},{"id":519199,"name":"Richard Z. Lin","orcid":"0000-0002-3967-0859","position":9,"is_corresponding":false},{"id":1328992,"name":"Han V. Han","orcid":null,"position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:56:09.638214Z","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":[]}