Furthermore, the high-mobility group box-1 (HMGB1) protein, a cytokine-like factor expressed by multiple mammalian cells, is known to be strongly up regulated in breast cancer, colon cancer, melanoma, pancreatic cancer, and prostate cancer, and this up regulation activates TLR2 and TLR4 expression in immune cells, thereby facilitating cancer progression and metastasis [53]. Here, TLR4 is linked to melanoma.