Local glycan engineering induces systemic antitumor immune reactions via antigen cross-presentation

Recent studies highlight the role of sialic acid-containing glycans and their interaction with sialic acid-binding immunoglobulin-like lectin (Siglec) receptors in the tumor microenvironment, offering a promising avenue for cancer immunotherapy. Myeloid cells, particularly tumor-associated macrophages (TAMs), mediate sialic acid-mediated immune suppression via Siglec receptors.

Different approaches, including antibodies, sialidases, and glycomimetics, can block the sialic acid-Siglec pathway, with promising results in preclinical models and ongoing clinical trials. However, achieving sufficiently high intratumoral sialidase levels without systemic toxicity remains a challenge.