{"doi":"10.1101/2023.09.14.557799","title":"Acod1 Expression in Cancer Cells Promotes Immune Evasion through the Generation of Inhibitory Peptides","abstract":"Abstract Targeting PD-1 is an important component of many immune checkpoint blockade (ICB) therapeutic approaches. However, ICB is not an efficacious strategy in a variety of cancer types, in part due to immunosuppressive metabolites in the tumor microenvironment (TME). Here, we find that αPD-1-resistant cancer cells produce abundant itaconate (ITA) due to enhanced levels of aconitate decarboxylase (Acod1). Acod1 has an important role in the resistance to αPD-1, as decreasing Acod1 levels in αPD-1 resistant cancer cells can sensitize tumors to αPD-1 therapy. Mechanistically, cancer cells with high Acod1 inhibit the proliferation of naïve CD8 + T cells through the secretion of inhibitory factors. Surprisingly, inhibition of CD8 + T cell proliferation is not dependent on secretion of ITA, but is instead a consequence of the release of small inhibitory peptides. Our study suggests that strategies to counter the activity of Acod1 in cancer cells may sensitize tumors to ICB therapy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400788,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9625,"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":473883,"name":"Joseph Longo","orcid":"0000-0002-9580-5105","position":1,"is_corresponding":false},{"id":503196,"name":"Ryan D. Sheldon","orcid":"0000-0002-1573-9719","position":2,"is_corresponding":false},{"id":1177509,"name":"Emma Albano","orcid":null,"position":3,"is_corresponding":false},{"id":1177510,"name":"Mark A. Hawk","orcid":null,"position":4,"is_corresponding":false},{"id":908945,"name":"Seán Murphy","orcid":"0000-0002-6582-4065","position":5,"is_corresponding":false},{"id":706113,"name":"Loan Duong","orcid":"0000-0003-4785-7194","position":6,"is_corresponding":false},{"id":449675,"name":"Sharif Rahmy","orcid":"0000-0002-7825-7186","position":7,"is_corresponding":false},{"id":274882,"name":"Xin Lü","orcid":"0000-0002-0284-6478","position":8,"is_corresponding":false},{"id":232805,"name":"Russell G. Jones","orcid":"0000-0003-2250-4675","position":9,"is_corresponding":false},{"id":993391,"name":"Zachary T. Schafer","orcid":"0000-0001-9227-3118","position":10,"is_corresponding":false},{"id":1121620,"name":"James H. Schofield","orcid":"0000-0002-7383-583X","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:04.010538Z","pmid":"37745450","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":[]}