Mechanistically, a regulatory network centred on SMAD3 is upregulated in MMTs in NSCLC, and chromatin immunoprecipitation sequencing (ChIP-seq) detected that SMAD3 is predominantly bound in fibroblast differentiation-related genes in macrophage lineage cells in Lewis lung carcinoma, and that macrophage-specific deletion and pharmacological inhibition of SMAD3 can effectively block MMT, thereby inhibiting TAF formation and cancer progression in vivo. Here, SMAD3 is linked to non-small cell lung carcinoma.