Sweet escape: Sialic acids in tumor immune evasion

• Published in: Biochimica et biophysica acta Vol. 1846; no. 1; pp. 238 - 246
• Main Authors: Büll, Christian, den Brok, Martijn H., Adema, Gosse J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2014
• Subjects: Animals; Cancer; Complement System Proteins - immunology; Complement System Proteins - metabolism; Dendritic Cells - immunology; Humans; Immune evasion; Immune System - metabolism; Immunotherapy; Myeloid Cells - immunology; Neoplasms - immunology; Neoplasms - therapy; Sialic acids; Sialic Acids - metabolism; Sialoglycans; Siglecs; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; Tumor Escape - immunology; Tumor microenvironment; MDSC; Tumor microenvironment; CTLs; Treg; Siglecs; Immune evasion; STn; Neu5Gc; TACA; Sialic acids; ITIMs; SAMPs; GBM; DISC; Sialoglycans; NK cell; NKT cell; SLeA/X; PSA; DC; Cancer
• ISSN: 0304-419X; 0006-3002; 1879-2561
• DOI: 10.1016/j.bbcan.2014.07.005

Sialic acids represent a family of sugar molecules derived from neuraminic acid that frequently terminate glycan chains and contribute to many biological processes. Already five decades ago, aberrantly high expression of sialic acids has been proposed to protect cancer cells from recognition and eradication by the immune system. Today, increased understanding at the molecular level demonstrates the broad immunomodulatory capacity of tumor-derived sialic acids that is, at least in part, mediated through interactions with immunoinhibitory Siglec receptors. Here we will review current studies from a sialic acid sugar perspective showing that tumor-derived sialic acids disable major killing mechanisms of effector immune cells, trigger production of immune suppressive cytokines and dampen activation of antigen-presenting cells and subsequent induction of anti-tumor immune responses. Furthermore, strategies to modulate sialic acid expression in cancer cells to improve cancer immunotherapy will be discussed. •Aberrant high expression of sialic acids on tumor cells facilitates immune evasion.•Tumors utilize the immune suppressive sialic acid/Siglec axis.•Tumor sialic acids protect from CTL and NK cell cytotoxicity.•Tumor sialoglycans modulate myeloid cell function and dampen dendritic cell activation.•Modulating aberrant sialylation in tumor cells could boost cancer immunotherapy.