CD4 and neoplasm: As stated above, a wealth of historical and more recent evidence now suggests that CD4+CD25high Treg cell populations influence the presence, induction, and maintenance of protective anti-tumor immunity (Raimondi et al., 2007; Facciabene et al., 2012; Lindau et al., 2013; Savage et al., 2013), and their association with the progression of malignant disease has been highlighted by a number of observations (Table 1).