Within the bone, RANK + DCs induce Treg cell expansion, which themselves serve as the key source for RANKL production in the presence of tumors, further inducing bone resorption that leads to local acidification of the bone microenvironment thereby activating TGF-β and generating more Tregs which promote tumor cell proliferation and growth within the bones (Huppert et al., 2022). This evidence concerns the gene TNFRSF11A and neoplasm.