Fig. 6: Dendrimers carrying a2,3 sialylated structures are able to modulate monocytes and macrophages.

A Monocytes were stimulated with a2,3 sialic acid dendrimers for four days in the presence or absence of M-CSF. B Expression of CD163, CD206 and PD-L1 in CD14⁺ cells after stimulation. Relative expression was calculated with respect to unstimulated monocytes. Data presented as mean values ± SEM. C Presence of IL-10 and IL-6 in supernatants was evaluated by ELISA. Data presented as mean values ± SEM. D Binding of Siglec-7 and Siglec-9 to sialic acid dendrimers. Data presented as mean values ± SEM. E Phospho-Immunoreceptor array of monocytes stimulated with α2,3 sialic acid and control dendrimers. F Expression of Siglec receptors in different monocyte-derived macrophages was evaluated by flow cytometry. G M-CSF monocyte-derived macrophages were stimulated with α2,3 sialic acid dendrimers in the presence or absence of LPS. H, I Expression of co-stimulatory markers (H) and cytokine production (I) after stimulation. In (H), relative expression was calculated with respect to unstimulated macrophages. Statistics: Pairwise comparisons of each condition against the respective control using Two-way ANOVA with Dunnett’s multiple comparisons test (*p ≤ 0.05; **p ≤ 0.01). J Scheme summarising the results of this paper. ① Circulating monocytes that infiltrate the tumour can interact with tumour-derived sialylated structures via the receptors Siglec-7 and Siglec-9. ② Triggering of Siglec receptors synergises with M-CSF to induce the differentiation of moMac and concomitant expression of IL-6 and IL-10. ③ Sialic acid triggering of Siglec-9 in moMac affects their expression of co-stimulatory molecules and cytokine production.