Upon homotypic targeting, siNNMT-CAF downregulated NNMT expression in CAFs, restored SAM and NAD+ levels, and epigenetically silenced the secretion of pro-stemness factors (IL-6, IL-8, CCL2) that normally sustain the CD44+CD133+ cancer stem cell (CSC) niche; concurrently, Chemo-CC eliminated tumor cells with high efficiency. Here, CCL2 is linked to neoplasm.