Ricerc@Sapienza

Microfluidics, the science and engineering of manipulating small amount of fluids within micrometre-sized devices, has a strongly multidisciplinary nature and is at the basis of the Lab-on-Chip (LoC) technology. Thanks to advancements in polymer engineering and to the development of soft lithography techniques, LoCs have become a valuable tool for biological applications, giving the possibility to mimic human patho-physiology by growing different cell populations in complex 3D microenvironment with physiologically relevant chemical and mechanical features. Such devices are widely employed in cancer research, as they allow to reproduce the heterogeneity of the tumour microenvironment (TME), a complex entity composed of several cell populations, contributing to tumour progression through several mechanisms, such as the impairment of dendritic cells (DC) capacity to trigger a proper immune response. In this context, microfluidic devices are valuable platforms to test innovative immunotherapeutic strategies, aimed at restoring an effective host immune response against cancer. For instance, the combination of the histone deacetylase inhibitor romidepsin (R) and IFN-alpha (I) has been demonstrated to be very effective in inducing the immunogenic cancer cells death while enhancing DCs capacity to uptake tumour antigens to trigger a proper immune response. Hence, aim of this project is to realise a microfluidic platform reproducing specific aspects of the TME, namely the tumour-vasculature interface, in order to evaluate the effect of RI on the recruitment of DCs to the tumour site, across the endothelial layer. Physiological levels of shear stress will be guaranteed by perfusing a constant flow within the vasculature, thus reproducing in vivo-like conditions, to which DCs are naturally exposed. DCs migratory behaviour and efficiency in crossing the endothelial layer will be characterised in order to assess the effectiveness of RI in enhancing DCs-mediated immune response.