GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE341nnn/GSE341382/primary200OKOtherMus musculusOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE341382GEOGSEfalseSpatial transcriptomics of mouse lung after tumor induction.Resistance to immune checkpoint blockade (ICB) remains a major barrier in non-small cell lung cancer (NSCLC), where defective antigen presentation, myeloid-cell dominance, and immune exclusion limit anti-tumor immunity. Here, we show that IL-12/FLT3L-armed dendritic-cell progenitors (DCPs) overcome these barriers by reprogramming the tumor microenvironment into an immune-responsive ecosystem dominated by interferon (IFN)-IRF1 signaling, which unlocked both chemo-immunotherapy and CAR-T efficacy in autochthonous and orthotopic KrasG12D;Trp53−/− lung tumors. DCP monotherapy triggered an IFN-stimulated gene (ISG) circuit operative across cellular compartments, while combination therapy enhanced tumor regression independent of MHC-I expression in cancer cells or CD8 T cell cytotoxicity. This response involved the expansion of IFNγ⁺ T and NK cells, inflammatory monocytes, ISG-polarized neutrophils, and immune-stimulatory fibroblasts, coupled with depletion of Tregs, immunosuppressive neutrophils, myofibroblasts, and angiogenic endothelial cells. IFNγ neutralization abrogated the therapeutic response, underscoring its central role in orchestrating cross-compartmental reprogramming. IRF1 was concordantly expressed across epithelial, immune, and stromal compartments in human cancer and correlated with ICB response, highlighting the relevance of DCP-induced inflammatory programs in cancer control.2026/09/15GSE341382GSM9905857GSM990585624247341382Mus musculus