Their polarization is shaped by ELR<sup>+</sup> CXC chemokines (CXCL1, CXCL8), cytokine signals, systemic inflammation, hypoxia driven by VHL/HIF pathways, and tumor-intrinsic oncogenic alterations such as PTEN loss, ERβ- and c-Myc-dependent programs, as well as epigenetic remodeling. This evidence concerns the gene ESR2 and neoplasm.