PO-392 Galectin-9 is required for dendritic cell function and directly contributes to DC-mediated anti-tumour immunity

Abstract

IntroductionDendritic cells (DCs) express a variety of cell surface receptors aimed at facilitating recognition, uptake and presentation of tumour antigens, which allows for the initiation of a potent anti-tumour immune response. Galectin-mediated interactions on DC-plasma membrane are emerging as potent modulators of cellular organisation although the underlying mechanisms are ill defined. We discovered that galectin-9 (gal-9) is required for DC phagocytosis and migration indicating that gal-9 controls tumour immune surveillance.Material and methodsResults and discussionsWe discovered a novel interaction between Galectin-9 and the phagocytic receptor DC-SIGN and demonstrated that galectin-9 is essential for DCs to take up antigens. Atomic force microscopy experiments uncovered that Galectin-9 directly controls plasma membrane stiffness via the reorganisation of the actin cytoskeleton.Moreover, we observed that galectin-9 is essential for chemokine-driven DC migration and for their capacity to react to melanoma cells, which may have direct implications for tumour immune surveillance. Supporting this hypothesis, we observed that the expression of galectin-9 is down-regulated in DCs upon co-culturing with melanoma tumour cells.ConclusionIn summary, our work identified Galectin-9 as novel plasma membrane organiser in DCs through reorganisation of the actin cytoskeleton that underlies plasma membrane rigidity. Furthermore, our data postulates galectin-9 as a key modulator of DC function, with implications in the ability of DCs to initiate an anti-tumour response. Based on our findings, we hypothesise that loss of galectin-9 impairs DCs to migrate and respond to tumours hampering anti-tumour immunity, thus facilitating tumour immune escape.