CCL2 production in the tumor-stroma setting was connected to pro-inflammatory conditions: pro-inflammatory stimuli (TNFα and IL-1β) have strongly up-regulated the release of CCL2 by tumor-stroma co-cultures (159), and in parallel CCL2 has induced an inflammatory TME in mice, demonstrated by high localization of macrophages and increased stroma and collagen density in mice (173). This evidence concerns the gene TNF and neoplasm.