Indeed, tumor cells secrete exosomes and secretory autophagosomes carrying endogenous TLR2 ligands (HMGB1, HSP72, HSP90, palmitoylated proteins and others) [40], which reach distant organs and, by activating the TLR2–IL-6–STAT3 signaling pathway in myeloid cells, promote the establishment of the pre-metastatic niche and contribute to the “seed and soil” mechanism responsible for metastasis development [43]. Here, HMGB1 is linked to neoplasm.