SPP1 and neoplasm: Through integrated analyses of scRNA-seq performed in this study, publicly accessible scRNA-seq and bulk RNA-seq datasets, spatial transcriptomics, FACS, IF, and transcriptomics with ICB treatment, our study provided a comprehensive picture of the landscape of TME and its adjacent normal tissue counterpart at the single-cell resolution, as well as demonstrating that the interaction between FAP+ fibroblasts and SPP1+ macrophages may play an instructive role in the formation of desmoplastic TME, which may lead to resistance to tumor immunotherapy.