Regarding extrinsic factors, infiltration and activation of M2 macrophages and Treg cells in tumor tissue and an increase in highly differentiated CD28−CD27−CD4+ T cells in peripheral blood have been identified in patients with HPD.[11–13] Th2 cytokines such as interleukin-4 and interleukin-13 induce differentiation from monocytes into M2 macrophages, which possess protumorigenic properties in tumor tissue. This evidence concerns the gene IL4 and neoplasm.