Preconditioning of human dendritic cells with hyaluronic acid increases their migration capacity in vitro and in vivo.

RIZZO MM; PICCIONI F; MALVICINI M; LLOYD R; GARCÍA MG; ATORRASAGASTI C; BAYO J; FIORE E; ANDRIANI O; TERRES M; GONZÁLEZ-CAMPAÑA A; PODESTÁ G; ALANIZ L; MAZZOLINI G

Conferencia; 9° Conferencia Internacional de Ácido hialurónico.; 2013

Dendritic cells (DCs) are the main cells responsible for initiating and coordinating the immune response to antigens, which have been used in cancer treatment. Once inoculated, the induced immune response depends, at least in part, on their ability to migrate to secondary lymphoid organs where they can trigger the antitumor response. The way in which they are cultures and cultivated prior to their use as therapeutic vaccines against cancer is very heterogeneous as are the results of its clinical use. Hyaluronic acid (HA)is the major component of the extracellular matrix and a regulator of several biological processes. Last decade several works have shown that HA is an important factor able to modulate immune response in both physiological and pathological condition. We previously have observed that inoculation of low molecular weight (LMW)HA in mice with colon carcinoma was able to stimulate tumor specific immune response. Therefore, we propose the use of LMW HA as a component of the "cocktail" of DC maturation in order to improve its efficiency to generate antitumor immunity. We focus on evaluating changes in migration capacity of DC using HA. Objective: to determine whether the use of HA is able to activate and modulate the migration capacity of DC pulsed with tumor antigen (DC/TL/HA)from both healthy volunteers and patients with metastatic colon tumors, and investigate which mechanisms could be involved. Methods: we assessed DC maturation markers by flow cytometry, performed in vitro and in vivo migration assays, study metalloproteinase 2 and 9 activity by zymography, and evaluated the expression of HA receptors potentially involved in this response by qPCR. Results: The DC/TL/HA derived from healthy volunteers shows a significant higher migration index toward CCL21 relative to untreated CD/TL, evaluated in vitro in a Boyden chamber. In vivo, in a nude mouse model, these cells have a greater capacity to migrate to lynmph nodes. The treatment with HA does not modify the CCR7 expression. However we evidenced that HA treatment increased the expression of MHC II but does not affect the expression of CD80, CD83, CD86 and CD40. Moreover, we observed that this treatment modulates the expression of TLR2 and CD44, receptors involved in HA signaling. These results were reproduced in 40% of DC/TL/HA derived from colon cancer patients, in which we observed an increase in their ability to migrate to CCL21 and MHC II expression. Conclusion: we suggest that HA could be an adjuvant in immunotherapy protocols enhancing their migration capacity and antigen presentation.