Sweet escape: Sialic acids in tumor immune evasion |
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Authors: | Christian Büll Martijn H den BrokGosse J Adema |
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Institution: | Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands |
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Abstract: | 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. |
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Keywords: | SLeA/X sialyl Lewis antigen A and X STn sialyl Tn antigen PSA polysialic acid SAMPs self-associated molecular patterns Siglecs sialic acid-binding immunoglobulin-like lectins ITIMs immunoreceptor tyrosine-based inhibitory motifs NK cell natural killer cell NKT cell natural killer T cell CTLs cytotoxic T cells DISC death-inducing signaling complex Treg regulatory T cell MDSC myeloid-derived suppressor cell DC dendritic cell Neu5Gc N-glycolylneuraminic acid TACA tumor-associated carbohydrate antigen GBM glioblastoma multifore |
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