The pleiotropic cytokine interleukin (IL)-21 has potent anti-tumor effects due to its ability to expand the pool of cytotoxic CD8+ T cells, NK cells and NKT cells [11] and beneficial IL-21-mediated anti-tumor responses have been documented in mice implanted with syngeneic tumor lines (including CRC cell lines) [12] as well as in patients with advanced solid tumors [13, 14]. This evidence concerns the gene CD8A and colorectal carcinoma.