{"doi":"10.1136/jitc-2022-005940","title":"Statin drugs enhance responses to immune checkpoint blockade in head and neck cancer models","abstract":"BACKGROUND: Anti-PD-1 immune checkpoint blockade is approved for first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but few patients respond. Statin drugs (HMG-CoA reductase inhibitors) are associated with superior survival in several cancer types, including HNSCC. Emerging data suggest that manipulation of cholesterol may enhance some aspects of antitumor immunity. METHODS: We used syngeneic murine models (mouse oral cancer, MOC1 and TC-1) to investigate our hypothesis that a subset of statin drugs would enhance antitumor immunity and delay tumor growth. RESULTS: Using an ex vivo coculture assay of murine cancer cells and tumor infiltrating lymphocytes, we discovered that all seven statin drugs inhibited tumor cell proliferation. Simvastatin and lovastatin also enhanced T-cell killing of tumor cells. In mice, daily oral simvastatin or lovastatin enhanced tumor control and extended survival when combined with PD-1 blockade, with rejection of MOC1 tumors in 30% of mice treated with lovastatin plus anti-PD-1. Results from flow cytometry of tumors and tumor-draining lymph nodes suggested T cell activation and shifts from M2 to M1 macrophage predominance as potential mechanisms of combination therapy. CONCLUSIONS: These results suggest that statins deserve further study as well-tolerated, inexpensive drugs that may enhance responses to PD-1 checkpoint blockade and other immunotherapies for HNSCC.","journal":"Journal for ImmunoTherapy of Cancer","year":2023,"id":316503,"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":100,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.961,"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":487158,"name":"Andre J. Burnham","orcid":"0000-0003-2541-5088","position":1,"is_corresponding":false},{"id":1007654,"name":"Brendan L. C. Kinney","orcid":"0000-0002-3516-3008","position":2,"is_corresponding":false},{"id":241868,"name":"Nabil F. Saba","orcid":"0000-0003-4972-1477","position":3,"is_corresponding":false},{"id":314041,"name":"Chrystal M. Paulos","orcid":"0000-0002-0784-2601","position":4,"is_corresponding":false},{"id":328027,"name":"Gregory B. Lesinski","orcid":"0000-0002-8787-7678","position":5,"is_corresponding":false},{"id":251257,"name":"Zachary S. Buchwald","orcid":"0000-0003-4407-7264","position":6,"is_corresponding":false},{"id":456242,"name":"Nicole C. Schmitt","orcid":"0000-0002-0571-3531","position":7,"is_corresponding":false},{"id":1007653,"name":"Vikash Kansal","orcid":"0000-0002-8240-2112","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T01:06:38.213358Z","pmid":"36650022","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":[]}