Sustained STAT3 activation leads to the proliferation of many tumor cells (75–78).The widespread expression of IL-21R in immune enables IL-21 to activate macrophage, DCs, NK cells, B cells, NK T cells, CD4+T cells, CD8+ T cells, Treg cells, Th17 cells, follicular helper T cells, etc. (78, 113, 117–122). This evidence concerns the gene CD4 and neoplasm.