In EMPD, for example, soluble RANKL released by Paget cells increases the production of CCL5, CCL17, and CXCL10 from RANK+ M2 polarized TAMs (8, 10, 17), suggesting that Paget cells can determine the immunological microenvironment by the stimulation of TAMs. This evidence concerns the gene TNFSF11 and extramammary Paget disease.