NF-κB regulates the expression of over 200 genes that control the immune system, cancer cell growth and inflammation [39]. Because of its abilities to induce the expression of a large array of inflammatory mediators and its roles as core transcription factors in diverse immune responses, NF-κB has been recognized as a major factor responsible for cytokine-associated cancer development or anti-tumor immunity. In the melanoma tumor tissues of the CCR5−/− mice, the expression of NF-κB target cell death genes (Bax, caspase-3 and 9) and the DNA binding activity of NF-κB, were significantly inhibited, but the expression of cell death inhibitory NF-κB target genes, such as Bcl-2 and cIAP were enhanced. In addition, CCR5−/− prevented the phosphorylation of IκB, accompanied with the inhibition of the p50 and p65 translocation into the nucleus (Figure 2A-C). Many tumors, including melanoma, have increased levels of NF-κB [40], which is likely acting as a survival factor for melanoma growth. Thus, the inhibitions of NF-κB activity and the expression of target genes are critical in the inhibition of tumor growth in CCR5−/− mice. Although the mechanism is not clear as to how CCR5−/− downregulates NF-κB, it is noteworthy that NF-κB is activated or inactivated by many cytokines.