Thus, it is tempting to speculate that an immune-suppressive loop may be triggered by HMGB1, which is over-expressed in different human tumors and correlates with tumor progression [83,84] through the induction of HLA-G expression upon the interaction with TLR-4 paralleled by the inhibition of anti-tumor T cell response upon TIM-3 ligation. This evidence concerns the gene HLA-G and neoplasm.