Based on spatial transcriptome and metabolic analysis of the TME of patients before and after ICIs treatment, SPP1+ macrophages can interact with tumor cells by activating COL11A1+ CAFs, stimulating collagen fibers to deposit and entangle at tumor boundaries, thus hindering T-cell infiltration and ultimately leading to poor response of NSCLC patients to anti-PD-1 therapy [127]. This evidence concerns the gene SPP1 and neoplasm.