{"doi":"10.1126/sciimmunol.adi5374","title":"TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti–PD-1 tumor immunotherapy","abstract":"The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti–programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti–PD-1. Here, we found that anti–PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of Ruminococcus gnavus in the gut microbiota. Gavage of wild-type mice with R. gnavus enhanced anti–PD-1–mediated tumor elimination, recapitulating the effect occurring in the absence of TREM2. A proinflammatory intestinal environment coincided with expansion, increased circulation, and migration of TNF-producing CD4 + T cells to the tumor bed. Thus, TREM2 remotely controls anti–PD-1 immune checkpoint blockade through modulation of the intestinal immune environment and microbiota, with R. gnavus emerging as a potential probiotic agent for increasing responsiveness to anti-PD-1.","journal":"Science Immunology","year":2024,"id":418628,"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":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":109966,"name":"Martina Molgora","orcid":"0000-0001-7328-2844","position":1,"is_corresponding":false},{"id":1202876,"name":"Darya Khantakova","orcid":"0000-0002-2579-5140","position":2,"is_corresponding":false},{"id":260038,"name":"Natália Jaeger","orcid":"0000-0003-2875-8297","position":3,"is_corresponding":false},{"id":1025723,"name":"Hao-Wei Chang","orcid":"0000-0002-1160-7452","position":4,"is_corresponding":false},{"id":252040,"name":"Rafael S. Czepielewski","orcid":"0000-0002-2475-3838","position":5,"is_corresponding":false},{"id":104273,"name":"Beth A. Helmink","orcid":"0000-0002-8206-0351","position":6,"is_corresponding":false},{"id":342538,"name":"Emily J. Onufer","orcid":"0000-0002-8802-5346","position":7,"is_corresponding":false},{"id":626288,"name":"José Luís Fachi","orcid":"0000-0002-1035-5193","position":8,"is_corresponding":false},{"id":1207094,"name":"Bishan Bhattarai","orcid":"0009-0003-1263-8554","position":9,"is_corresponding":false},{"id":882286,"name":"Tihana Tršan","orcid":"0000-0002-7549-2885","position":10,"is_corresponding":false},{"id":478921,"name":"Patrick Fernandes Rodrigues","orcid":"0000-0002-0214-0627","position":11,"is_corresponding":false},{"id":71128,"name":"Jinchao Hou","orcid":"0000-0003-3829-7551","position":12,"is_corresponding":false},{"id":249173,"name":"Jennifer K. Bando","orcid":"0000-0002-1331-7424","position":13,"is_corresponding":false},{"id":1207095,"name":"Cristiane Sécca","orcid":"0000-0003-4433-8962","position":14,"is_corresponding":false},{"id":109978,"name":"Marina Cella","orcid":"0000-0003-1230-1313","position":15,"is_corresponding":false},{"id":109979,"name":"Susan Gilfillan","orcid":"0000-0003-1672-0996","position":16,"is_corresponding":false},{"id":1018761,"name":"Robert D. Schreiber","orcid":"0000-0001-6311-0432","position":17,"is_corresponding":false},{"id":19791,"name":"Jeffrey I. Gordon","orcid":"0000-0001-8304-3548","position":18,"is_corresponding":false},{"id":71132,"name":"Marco Colonna","orcid":"0000-0001-5222-4987","position":19,"is_corresponding":false},{"id":314945,"name":"Blanda Di Luccia","orcid":"0000-0002-0137-953X","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T01:57:09.067930Z","pmid":"38758808","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":[]}