{"doi":"10.1038/s41586-021-03626-9","title":"TIM-3 restrains anti-tumour immunity by regulating inflammasome activation","abstract":"T cell immunoglobulin and mucin-containing molecule 3 (TIM-3), first identified as a molecule expressed on interferon-γ producing T cells<sup>1</sup>, is emerging as an important immune-checkpoint molecule, with therapeutic blockade of TIM-3 being investigated in multiple human malignancies. Expression of TIM-3 on CD8<sup>+</sup> T cells in the tumour microenvironment is considered a cardinal sign of T cell dysfunction; however, TIM-3 is also expressed on several other types of immune cell, confounding interpretation of results following blockade using anti-TIM-3 monoclonal antibodies. Here, using conditional knockouts of TIM-3 together with single-cell RNA sequencing, we demonstrate the singular importance of TIM-3 on dendritic cells (DCs), whereby loss of TIM-3 on DCs-but not on CD4<sup>+</sup> or CD8<sup>+</sup> T cells-promotes strong anti-tumour immunity. Loss of TIM-3 prevented DCs from expressing a regulatory program and facilitated the maintenance of CD8<sup>+</sup> effector and stem-like T cells. Conditional deletion of TIM-3 in DCs led to increased accumulation of reactive oxygen species resulting in NLRP3 inflammasome activation. Inhibition of inflammasome activation, or downstream effector cytokines interleukin-1β (IL-1β) and IL-18, completely abrogated the protective anti-tumour immunity observed with TIM-3 deletion in DCs. Together, our findings reveal an important role for TIM-3 in regulating DC function and underscore the potential of TIM-3 blockade in promoting anti-tumour immunity by regulating inflammasome activation.","journal":"Nature","year":2021,"id":8158,"datarank":0.8845730801455112,"base_score":5.8971538676367405,"endowment":5.8971538676367405,"self_citation_contribution":0.8845730801455112,"citation_network_contribution":0.0,"self_endowment_contribution":0.8845730801455112,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":363,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0447,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-06-09","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":2687,"name":"Marcin Tabaka","orcid":"0000-0002-6166-2820","position":1,"is_corresponding":false},{"id":14740,"name":"Markus A. Schramm","orcid":"0000-0003-3513-3842","position":2,"is_corresponding":false},{"id":7856,"name":"Sheng Xiao","orcid":"0000-0001-6252-8204","position":3,"is_corresponding":false},{"id":7822,"name":"Ruihan Tang","orcid":"0000-0001-5250-6239","position":4,"is_corresponding":false},{"id":2276,"name":"Danielle Dionne","orcid":"0000-0002-8338-4323","position":5,"is_corresponding":false},{"id":3016,"name":"Ana. C. Anderson","orcid":"0000-0002-0877-2932","position":6,"is_corresponding":false},{"id":2697,"name":"Orit Rozenblatt–Rosen","orcid":"0000-0001-6313-3570","position":7,"is_corresponding":false},{"id":29633,"name":"Prisca Liberali","orcid":"0000-0003-0695-6081","position":8,"is_corresponding":false},{"id":6940,"name":"Vijay K. Kuchroo","orcid":"0000-0001-7177-2110","position":9,"is_corresponding":false},{"id":7816,"name":"Karen O. Dixon","orcid":"0000-0001-7811-5439","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":[]}