Using single-cell RNA sequencing (scRNA-seq) analysis from public database, patient-derived organoid models, and <i>in vivo</i> mouse models, we demonstrated that IGLC3<sup>-</sup> tumor cells secreted TGF-β to polarize M0 macrophages into an SPP1<sup>+</sup>, M2-like phenotype. The gene discussed is SPP1; the disease is neoplasm.