In order to identify a novel and more effective therapy for this disease, we adopted a gene transfer strategy into mouse hematopoietic stem/progenitor cells to generate immune‐competent mice in which TEMs—a Tie2+ subset of monocytes/macrophages found at peritumoral sites—express interferon‐alpha (IFNα), a pleiotropic cytokine with anti‐tumor effects, to verify the impact of such approach in mouse models of CRC liver metastases. This evidence concerns the gene IFNA1 and neoplasm.