These receptors belong to a large family of membrane proteins with cytoplasmic signaling domains and extracellular domains capable of recognizing pathogen-associated molecular patterns. Segal et al. have followed the expression of these CX-4945 molecules during the differentiation process of monocytes to activated dendritic cells. Down-regulation of these receptors might suggest a mature DC phenotype as it was demonstrated in LPS stimulated DC. Therefore, it seems that LMW HA has a stimulatory effect on DC pulsed with tumor lysate in both HD and CRC patients. Clinical application of DC-based cancer vaccines has been limited due to their weak efficacy. One limitation might be related to the failure of DC to reach secondary lymphoid organs. It is known that only a small percentage of inoculated DC migrate toward the lymph nodes where they could activate naı ¨ve T cells. Once DC are inoculated they undergo a kind of conflicting force attraction between tumoral- and lymphoidderived chemokines. This contrary stimulus and the specific repertoire receptors expressed by DC determine whether they would migrate to the lymph node or to tumors. It has been shown that different DC maturation stimuli such as IL1b, TNF-a, PGE2 or poly induce the expression of CCR7 which enhances DC migration response toward lymph node. However, those molecules might exert a negative effect on DC in different ways. For example, it was shown that PGE2 and Poly can induce a tolerogenic state on DC. Moreover, some studies reported that LPS and poly can induce inhibitory effects on DC by activation SOCS signals. We have herein shown in vitro evidences that LMW HA pre-conditioning enhances DC migration to CCL21 and inhibits their attraction toward IL-8. Despite it is likely that many molecules involved in DC migration do not cross-react across species differences, we demonstrated in vitro and in vivo that DC/TL/LMW HA increase their migration toward LNCM from tumor bearing mice and lymph node, respectively. In addition their attraction to TCM and tumor tissue was also diminished. These phenomena seem to be at least partially mediated by upregulation of CCR7 expression levels, which is the main receptor of CCL19 and CCL21. This cytokine is expressed by lymphatic endothelial and lymph node stromal cells, and was shown essential to attract DC toward them. Another mechanism that might affect DC recruitment toward the lymph node is the capacity to digest extracellular matrix by MMPs, thus facilitating migration through connective tissues and crossing basement membranes. MMPs also act cleaving cell surface receptors or their ligands, promoting migration by releasing or activating ligands for receptors that control cell motility, or suppressing migration by inactivating chemokines. In line with this, Ratzinger et al. demonstrated that MMP-2 and MMP-9 are involved in the emigration of DC from epidermal skin explants as well as dermal DC from the dermis.