Targeting the Siglec/sialic-acid axis in glioblastoma: Glycome-mediated immune evasion and emerging therapeutic platforms

Abstract

Abstract Despite encouraging advances in cancer immunotherapy, several malignancies leverage resistance pathways to escape the effects of treatment. Abnormal cell signaling and cytokine secretion modulated by cancer cells promote a tumor microenvironment (TME), wherein the efficacy of infiltrating immune cells is diminished. There is increasing evidence that alteration of the glycosylation profile of some TMEs is a key factor in exhausting the immune response. The sialic-acid/Siglec axis has received attention for its suspected involvement in this context through both preclinical study and several clinical trials. Against this backdrop, glioblastoma (GBM) is a well-established immune-suppressive tumor with disappointing responses to most traditional immunotherapies. Recent studies have suggested that GBM can exploit the sialic-acid/Siglec axis to promote immune evasion and resistance to traditional immune checkpoint inhibitors. This review examines all presently identified Siglec interactions and the current state of Siglec-centered therapies with respect to GBM.