{"doi":"10.1016/j.cmet.2023.06.005","title":"Immunometabolic coevolution defines unique microenvironmental niches in ccRCC","abstract":"Tumor cell phenotypes and anti-tumor immune responses are shaped by local metabolite availability, but intratumoral metabolite heterogeneity (IMH) and its phenotypic consequences remain poorly understood. To study IMH, we profiled tumor/normal regions from clear cell renal cell carcinoma (ccRCC) patients. A common pattern of IMH transcended all patients, characterized by correlated fluctuations in the abundance of metabolites and processes associated with ferroptosis. Analysis of intratumoral metabolite-RNA covariation revealed that the immune composition of the microenvironment, especially the abundance of myeloid cells, drove intratumoral metabolite variation. Motivated by the strength of RNA-metabolite covariation and the clinical significance of RNA biomarkers in ccRCC, we inferred metabolomic profiles from the RNA sequencing data of ccRCC patients enrolled in 7 clinical trials, and we ultimately identifyied metabolite biomarkers associated with response to anti-angiogenic agents. Local metabolic phenotypes, therefore, emerge in tandem with the immune microenvironment, influence ongoing tumor evolution, and are associated with therapeutic sensitivity.","journal":"Cell Metabolism","year":2023,"id":332839,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9385,"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":673690,"name":"Amy Xie","orcid":"0000-0002-1441-7849","position":1,"is_corresponding":false},{"id":13129,"name":"Eric Minwei Liu","orcid":"0000-0002-3594-6678","position":2,"is_corresponding":false},{"id":244688,"name":"Fengshen Kuo","orcid":"0000-0003-1797-2896","position":3,"is_corresponding":false},{"id":898729,"name":"Min‐Soo Kim","orcid":"0000-0001-8760-4568","position":4,"is_corresponding":false},{"id":314352,"name":"Renzo G. DiNatale","orcid":"0000-0002-7867-2881","position":5,"is_corresponding":false},{"id":616271,"name":"Mahdi Golkaram","orcid":"0000-0002-8981-0047","position":6,"is_corresponding":false},{"id":249413,"name":"Ying‐Bei Chen","orcid":"0000-0001-5207-3648","position":7,"is_corresponding":false},{"id":348095,"name":"Sounak Gupta","orcid":"0000-0001-5163-6955","position":8,"is_corresponding":false},{"id":226686,"name":"Robert J. Motzer","orcid":"0000-0001-6925-2327","position":9,"is_corresponding":false},{"id":348101,"name":"Paul Russo","orcid":"0000-0001-7487-6783","position":10,"is_corresponding":false},{"id":90753,"name":"Jonathan Coleman","orcid":"0000-0002-6428-7835","position":11,"is_corresponding":false},{"id":337832,"name":"Maria I. Carlo","orcid":"0000-0002-4786-7408","position":12,"is_corresponding":false},{"id":289279,"name":"Martin H. Voss","orcid":"0000-0003-0551-5807","position":13,"is_corresponding":false},{"id":348094,"name":"Ritesh R. Kotecha","orcid":"0000-0002-0223-3479","position":14,"is_corresponding":false},{"id":470240,"name":"Chung‐Han Lee","orcid":"0000-0001-5511-0635","position":15,"is_corresponding":false},{"id":539622,"name":"Wesley Tansey","orcid":"0000-0002-5294-4228","position":16,"is_corresponding":false},{"id":1863,"name":"Nikolaus Schultz","orcid":"0000-0002-0131-4904","position":17,"is_corresponding":false},{"id":90737,"name":"A. Ari Hakimi","orcid":"0000-0002-0930-8824","position":18,"is_corresponding":false},{"id":69726,"name":"Ed Reznik","orcid":"0000-0002-6511-5947","position":19,"is_corresponding":false},{"id":843216,"name":"Cerise Tang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:09:35.125543Z","pmid":"37413991","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":[]}