{"doi":"10.1016/j.ccell.2025.04.003","title":"Spatial and multiomics analysis of human and mouse lung adenocarcinoma precursors reveals TIM-3 as a putative target for precancer interception","abstract":"How tumor microenvironment shapes lung adenocarcinoma (LUAD) precancer evolution remains poorly understood. Spatial immune profiling of 114 human LUAD and LUAD precursors reveals a progressive increase of adaptive response and a relative decrease of innate immune response as LUAD precursors progress. The immune evasion features align the immune response patterns at various stages. TIM-3-high features are enriched in LUAD precancers, which decrease in later stages. Furthermore, single-cell RNA sequencing (scRNA-seq) and spatial immune and transcriptomics profiling of LUAD and LUAD precursor specimens from 5 mouse models validate high TIM-3 features in LUAD precancers. In vivo TIM-3 blockade at precancer stage, but not at advanced cancer stage, decreases tumor burden. Anti-TIM-3 treatment is associated with enhanced antigen presentation, T cell activation, and increased M1/M2 macrophage ratio. These results highlight the coordination of innate and adaptive immune response/evasion during LUAD precancer evolution and suggest TIM-3 as a potential target for LUAD precancer interception.","journal":"Cancer Cell","year":2025,"id":509705,"datarank":0.5050943744979712,"base_score":3.367295829986474,"endowment":3.367295829986474,"self_citation_contribution":0.5050943744979712,"citation_network_contribution":0.0,"self_endowment_contribution":0.5050943744979712,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":461642,"name":"Pingjun Chen","orcid":"0000-0003-0528-1713","position":1,"is_corresponding":false},{"id":5675,"name":"Muhammad Aminu","orcid":"0000-0002-9903-8812","position":2,"is_corresponding":false},{"id":236198,"name":"Jiànróng Lǐ","orcid":"0000-0002-7130-1084","position":3,"is_corresponding":false},{"id":69930,"name":"Junya Fujimoto","orcid":"0000-0003-4813-3163","position":4,"is_corresponding":false},{"id":678161,"name":"Yanhua Tian","orcid":"0000-0001-7095-8765","position":5,"is_corresponding":false},{"id":247600,"name":"Lingzhi Hong","orcid":"0000-0001-6553-3279","position":6,"is_corresponding":false},{"id":680436,"name":"Hong Chen","orcid":"0000-0001-8054-7417","position":7,"is_corresponding":false},{"id":532244,"name":"Xin Hu","orcid":"0000-0003-1097-3300","position":8,"is_corresponding":false},{"id":1364734,"name":"Chenyang Li","orcid":"0000-0002-9144-5827","position":9,"is_corresponding":false},{"id":4544,"name":"Natalie I. 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