{"doi":"10.1016/j.celrep.2023.112303","title":"Saturated fatty acids dampen the immunogenicity of cancer by suppressing STING","abstract":"Oncogenes destabilize STING in epithelial cell-derived cancer cells, such as head and neck squamous cell carcinomas (HNSCCs), to promote immune escape. Despite the abundance of tumor-infiltrating myeloid cells, HNSCC presents notable resistance to STING stimulation. Here, we show how saturated fatty acids in the microenvironment dampen tumor response to STING stimulation. Using single-cell analysis, we found that obesity creates an IFN-I-deprived tumor microenvironment with a massive expansion of suppressive myeloid cell clusters and contraction of effector T cells. Saturated fatty acids, but not unsaturated fatty acids, potently inhibit the STING-IFN-I pathway in HNSCC cells. Myeloid cells from obese mice show dampened responses to STING stimulation and are more suppressive of T cell activation. In agreement, obese hosts exhibited increased tumor burden and lower responsiveness to STING agonist. As a mechanism, saturated fatty acids induce the expression of NLRC3, depletion of which results in a T cell inflamed tumor microenvironment and IFN-I-dependent tumor control.","journal":"Cell Reports","year":2023,"id":324980,"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":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9399,"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":663381,"name":"Wang Gong","orcid":"0000-0002-2116-3453","position":1,"is_corresponding":false},{"id":1041844,"name":"Hülya F. Taner","orcid":"0000-0002-8928-9829","position":2,"is_corresponding":false},{"id":1041845,"name":"Luke J. Broses","orcid":"0000-0003-2015-2928","position":3,"is_corresponding":false},{"id":1041846,"name":"Kohei Okuyama","orcid":"0000-0002-5616-902X","position":4,"is_corresponding":false},{"id":1042414,"name":"Wanqing Cheng","orcid":null,"position":5,"is_corresponding":false},{"id":1042415,"name":"Max Jin","orcid":null,"position":6,"is_corresponding":false},{"id":718222,"name":"Zackary R. Fitzsimonds","orcid":"0000-0002-6523-4911","position":7,"is_corresponding":false},{"id":823474,"name":"Andriana Manousidaki","orcid":"0000-0001-9213-795X","position":8,"is_corresponding":false},{"id":1041847,"name":"Yuesong Wu","orcid":"0000-0002-5931-6670","position":9,"is_corresponding":false},{"id":292346,"name":"Shaoping Zhang","orcid":"0000-0003-3004-4023","position":10,"is_corresponding":false},{"id":515128,"name":"Haitao Wen","orcid":"0000-0002-6363-2748","position":11,"is_corresponding":false},{"id":304744,"name":"Steven B. Chinn","orcid":"0000-0003-4282-0640","position":12,"is_corresponding":false},{"id":454361,"name":"Eric Bartee","orcid":"0000-0003-1793-446X","position":13,"is_corresponding":false},{"id":544174,"name":"Yuying Xie","orcid":"0000-0002-1049-2219","position":14,"is_corresponding":false},{"id":249124,"name":"James J. Moon","orcid":"0000-0003-2238-2372","position":15,"is_corresponding":false},{"id":109672,"name":"Yu L. Lei","orcid":"0000-0002-9868-9824","position":16,"is_corresponding":false},{"id":464129,"name":"Blake R. Heath","orcid":"0000-0001-8656-0532","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T01:08:16.809511Z","pmid":"36952341","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":[]}