{"doi":"10.1172/jci131859","title":"Targeting glutamine metabolism enhances tumor-specific immunity by modulating suppressive myeloid cells","abstract":"Myeloid cells comprise a major component of the tumor microenvironment (TME) that promotes tumor growth and immune evasion. By employing a small-molecule inhibitor of glutamine metabolism, not only were we able to inhibit tumor growth, but we markedly inhibited the generation and recruitment of myeloid-derived suppressor cells (MDSCs). Targeting tumor glutamine metabolism led to a decrease in CSF3 and hence recruitment of MDSCs as well as immunogenic cell death, leading to an increase in inflammatory tumor-associated macrophages (TAMs). Alternatively, inhibiting glutamine metabolism of the MDSCs themselves led to activation-induced cell death and conversion of MDSCs to inflammatory macrophages. Surprisingly, blocking glutamine metabolism also inhibited IDO expression of both the tumor and myeloid-derived cells, leading to a marked decrease in kynurenine levels. This in turn inhibited the development of metastasis and further enhanced antitumor immunity. Indeed, targeting glutamine metabolism rendered checkpoint blockade-resistant tumors susceptible to immunotherapy. Overall, our studies define an intimate interplay between the unique metabolism of tumors and the metabolism of suppressive immune cells.","journal":"Journal of Clinical Investigation","year":2020,"id":48379,"datarank":6.623938941545007,"base_score":6.095824562432225,"endowment":6.095824562432225,"self_citation_contribution":0.9143736843648338,"citation_network_contribution":5.709565257180174,"self_endowment_contribution":0.9143736843648338,"citer_contribution":5.709565257180174,"corpus_percentile":null,"corpus_rank":null,"citation_count":443,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":228361,"name":"Im‐Hong Sun","orcid":"0000-0003-0288-2062","position":1,"is_corresponding":false},{"id":228362,"name":"Liang Zhao","orcid":"0000-0002-2126-6778","position":2,"is_corresponding":false},{"id":228363,"name":"Robert D. Leone","orcid":"0000-0002-1664-0075","position":3,"is_corresponding":false},{"id":229833,"name":"Im-Meng Sun","orcid":null,"position":4,"is_corresponding":false},{"id":228364,"name":"Wei Xu","orcid":"0000-0001-5404-7523","position":5,"is_corresponding":false},{"id":228365,"name":"Samuel L. Collins","orcid":"0000-0003-1340-8796","position":6,"is_corresponding":false},{"id":228366,"name":"Ada Tam","orcid":"0000-0001-6828-5290","position":7,"is_corresponding":false},{"id":228367,"name":"Richard L. Blosser","orcid":"0000-0002-8606-769X","position":8,"is_corresponding":false},{"id":229834,"name":"Chirag H. Patel","orcid":null,"position":9,"is_corresponding":false},{"id":228368,"name":"Judson M. Englert","orcid":"0000-0003-0235-2782","position":10,"is_corresponding":false},{"id":228369,"name":"Matthew L. Arwood","orcid":"0000-0003-4737-9786","position":11,"is_corresponding":false},{"id":41931,"name":"Jiayu Wen","orcid":"0000-0003-1249-6456","position":12,"is_corresponding":false},{"id":229835,"name":"Yee Chan‐Li","orcid":null,"position":13,"is_corresponding":false},{"id":228370,"name":"Lukáš Tenora","orcid":"0000-0002-6982-3545","position":14,"is_corresponding":false},{"id":228371,"name":"Pavel Majer","orcid":"0000-0002-1804-6934","position":15,"is_corresponding":false},{"id":228372,"name":"Rana Rais","orcid":"0000-0003-4059-2453","position":16,"is_corresponding":false},{"id":228373,"name":"Barbara S. Slusher","orcid":"0000-0001-9814-4157","position":17,"is_corresponding":false},{"id":228374,"name":"Maureen R. Horton","orcid":"0000-0002-0621-1015","position":18,"is_corresponding":false},{"id":228375,"name":"Jonathan D. Powell","orcid":"0000-0002-0850-2852","position":19,"is_corresponding":false},{"id":228360,"name":"Min Hee Oh","orcid":"0000-0003-1581-4288","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T20:34:12.647743Z","pmid":"32324593","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":[]}