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van de Wall, Stephanie; Santegoets, Kim C.M.; van Houtum, Eline J.H.; Büll, Christian; Adema, Gosse J.
Trends in immunology, April 2020, 2020-04-00, 20200401, Letnik: 41, Številka: 4Journal Article
Sialic acid sugar-carrying glycans, sialoglycans, are aberrantly expressed on many tumor cells and have emerged as potent regulatory molecules involved in creating a tumor-supportive microenvironment. Sialoglycans can be recognized by sialic acid-binding immunoglobulin-like lectins (Siglecs), a family of immunomodulatory receptors. Most mammalian Siglecs transmit inhibitory signals comparable with the immune checkpoint inhibitor programmed death protein 1 (PD-1), but some are activating. Recent studies have shown that tumor cells can exploit sialoglycan–Siglec interactions to modulate immune cell function, contributing to an immunosuppressive tumor microenvironment (TME). Interference with sialoglycan synthesis or sialoglycan–Siglec interactions might improve antitumor immunity. Many questions regarding specificity, signaling, and regulatory function of sialoglycan–Siglec interactions remain. We posit that sialoglycans and Siglecs present as potential glyco-immune ‘checkpoints’ for cancer immunotherapy. Aberrant sialic acid sugar expression is commonly found in different cancer types and immune cells express immunomodulatory Siglec receptors that can recognize these sialic acids in humans and mice. Recently, high expression of Siglecs was found on several immune cells within the tumor microenvironment (TME).Recent studies, using human samples and mouse models, indicate that sialoglycan–Siglec interactions in the TME can suppress effector immune cell activity and modulate myeloid cell functions, thus contributing to tumor immune evasion and sustained tumor growth.The individual contribution of the 14 Siglec family members to immune evasion and their precise sialoglycan ligands in the TME remain to be elucidated.Sialoglycans and Siglecs might represent immune ‘checkpoints’ that should be further explored as potential targets for cancer immunotherapy.
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in: SICRIS
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