Since Hisada et al. first evaluated the antitumor efficacy of IL-27 in 2004 [41], accumulating evidence has revealed that IL-27 has a potent antitumor activity, which is mediated by a variety of mechanisms including CD8+T cells [41–45], NK cells [46–48], antibody-dependent cell-mediated cytotoxicity (ADCC) [49], antiangiogenesis [50], direct suppression of tumor growth [51], and inhibition of cychroxygenase-2 (COX-2) expression [52], depending on the characteristics of individual tumors (Figure 2). The gene discussed is CD8A; the disease is neoplasm.