After TFF3 depletion, the expression of M2 markers (CD163, CD206, ARG-1, and IL-10) and S100A4 and S100A8 were remarkably downregulated (Fig. 5i, j), which confirmed our hypotheses that iCCA cells induce the M2 phenotype and pro-tumor polarization of resident macrophages by secreting TFF proteins. This evidence concerns the gene S100A4 and neoplasm.