{"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_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-06-09","fair_score":73.75,"fair_percentile":99.14248021108179,"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. 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