The sialic acid-Siglec immune checkpoint: an opportunity to enhance immune responses and therapy effectiveness in melanoma

Abstract Modulation of immune responses through immune checkpoint blockade has revolutionized cutaneous melanoma treatment. However, still not all patients successfully respond to these therapies, indicating the presence of yet unknown resistance mechanisms. Hence, it is crucial to find novel targets to improve therapy efficacy. One of the described resistance mechanisms is regulated by immune inhibitory Siglec receptors, that are engaged by the carbohydrates sialic acids expressed on tumor cells, contributing to PD1-like immune suppression mechanisms. In this review, we provide an overview on the regulation of sialic acid synthesis, its expression in melanoma, and the contribution of the sialic acid-Siglec axis to tumor development and immune suppressive mechanisms in the tumor microenvironment. Finally, we highlight potential sialic acid-Siglec axis related therapeutics to improve the treatment of melanoma.