CD28 and neoplasm: Accordingly, a recent report revealed that effector CD8+ T cells differentiate into CD27- CD28- or CD27+ CD28+ TEMRA cells based on the strength of TCR engagement and the immunogenicity of the tumor antigens (91) (Figure 1), while other studies have shown that the lack of CD27 and CD28 surface molecules is associated with the expression of p16 and p21 proteins, causing G1 cell cycle arrest and replicative senescence (86, 87) (Table 1).