Spatial and multiomics analysis of human and mouse lung adenocarcinoma precursors reveals TIM-3 as a putative target for precancer interception by Bo Zhu, Pingjun Chen,Muhammad Aminu, ...,Alexandre Reuben, Jia Wu,Jianjun Zhang instant download

Spatial and multiomics analysis of human and mouse lung adenocarcinoma precursors reveals TIM-3 as a putative target for precancer interception by Bo Zhu, Pingjun Chen,Muhammad Aminu, ...,Alexandre Reuben, Jia Wu,Jianjun Zhang instant download

SUMMARYHow tumor microenvironment shapes lung adenocarcinoma (LUAD) precancer evolution remains poorly understood. Spatial immune profiling of 114 human LUAD and LUAD precursors reveals a progressive increaseof adaptive response and a relative decrease of innate immune response as LUAD precursors progress. Theimmune 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 specimensfrom 5 mouse models validate high TIM-3 features in LUAD precancers. In vivo TIM-3 blockade at precancerstage, but not at advanced cancer stage, decreases tumor burden. Anti-TIM-3 treatment is associated withenhanced antigen presentation, T cell activation, and increased M1/M2 macrophage ratio. These resultshighlight 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.