One possible explanation for the inhibitory effect of HMGB1 in the tumor milieu might be that tumor-infiltrating pDCs highly express the T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), which binds HMGB1 with an affinity similar to that of RAGE and inhibits nucleic acid trafficking into endosomes leading to impaired TLR-mediated responses of mouse pDCs [118]. Here, HMGB1 is linked to neoplasm.