In many clinical settings, high levels of HMGB1 (both intra-tumoral and circulating) have negative prognostic or predictive value; where extracellular HMGB1 secreted by cancer cells can activate proinflammatory signaling pathways promoting tumor growth, metastasis, angiogenesis, and inhibition of CTL-dependent anti-tumor immunity by activation of Tregs and MDSCs. This evidence concerns the gene HMGB1 and cancer.