IL-8, a molecule shown to inhibit antitumor immune responses when it was peri/intra-tumoraly injected. Hyaluronic acid is a lineal, large and ubiquitous glycosaminoglycan with a simple chemical BAY-60-7550 structure found mainly in tissues undergoing cell proliferation, regeneration and repair. HA functions are well known to be size-dependent and the LMW HA form has been shown to induce the expression of proinflammatory genes such as IL-8, IL-12, TNF-a and inducible NO synthase in many types of cells including DC. In addition, LMW HA or its small fragments were shown to stimulate T cell responses by activating and up-regulating co-stimulatory molecules on DC in a CD44-independent and TLR4-dependent manner. Moreover, it has also been demonstrated that LMW HA can act as an adjuvant promoting antigen-specific T cell responses in vivo through TLR2 stimulation. The aim of this work was to evaluate the effects of LMW HA pre-conditioning on tumor-pulsed human DC obtained from both healthy donors and CRC patients. We found that LMW HA induced DC/TL maturation state able to enhance lymphocyte proliferation, and most importantly increasing their migratory capacity and avoiding tumor tissue attraction. These results provide the rationale for the potential use of LMW HA as an immunostimulatory molecule for DC-based vaccines protocols in the treatment of cancer patients. Our previous results showed that pre-incubation of DC with LMW HA was able to induce an efficient antitumoral effect in a CRC mouse model which was found to be mediated by the stimulation of DC maturation and activation, as well as by the induction of a potent migratory capacity towards lymphoid areas in vitro and in vivo. In the present study we demonstrated that LMW HA represents a potent stimulator of migration toward lymph node for human DC obtained from both HD and CRC patients, likely partially involving CCR7/CCL21 axis and inducing resistance to IL-8, a tumor-derived DC chemoattractant. In addition, LMW HA treatment enhanced MLR-stimulating capacity of DC in an in vivo assay. Thus, this work adds new data regarding the ability of LMW HA to improve migratory capacity of DC that could be relevant in future design of potential cancer vaccines protocols. Different studies showed that oligosaccharides of HA, but not high molecular weight HA, can be used to stimulate immune responses involving DC activation. Nevertheless, this is the first report addressing LMW HA effects on DC derived from patients with cancer and on their migratory response to lymph node signals. As expected, DC/TL from HD showed higher expression levels of maturation markers than those obtained from CRC patients. LMW HA was able to induce stimulatory effects on DC promoting an up-regulation of MHC-II and the co-stimulatory molecule CD86 when obtained from HD samples but not in those from CRC patients. This result could be, at least in part, due to the immunosuppressive state of cancer patients.