IL6 and cancer: SPP1/Spp1 production in TAM can be regulated by several factors (Figure 1C), including tumor necrosis factor (TNF), interleukin 6 (IL‐6), interleukin 1b (IL‐1b), lipopolysaccharide (LPS), colony‐stimulating factor 2 (CSF2, GM‐CSF),[23] macrophage migration inhibitory factor (MIF)[24] and hypoxia[1, 25] or inversely by interferon regulatory factor 8 (IRF8).[26, 27] In turn, SPP1 expression leads to the production of osteopontin, a molecule with pleiotropic effects,[23] and globally promoting different hallmarks of cancer (Figure 1C).