IFN,58,173 TNF-α,174 and blockade of TGF-β can induce N1 polarization.103 In contrast, TGF-β,2 IL-17,175 and G-CSF can induce N2 polarization.176 Furthermore, the source of TANs, NDNs, exhibits tumor-induced phenotypic plasticity, which can be induced by tumor-regulated mediators and CXCL1 to transition to a low-density state.56 The latter acquire the morphological, functional activity, and surface receptor expression characteristics of LDNs, indicating that LDNs may be partially derived from phenotype-changing NDNs56 (Fig. 2). This evidence concerns the gene TNF and neoplasm.