Sialoadhesin (CD169/Siglec-1) is an extended molecule that escapes inhibitory cis-interactions and synergizes with other macrophage receptors to promote phagocytosis

Klaas, M; Dubock, S; Ferguson, DJP; Crocker, PR

Women's Health Collection

Journal article

Sialoadhesin (CD169/Siglec-1) is an extended molecule that escapes inhibitory cis-interactions and synergizes with other macrophage receptors to promote phagocytosis

Abstract:: The first generation of immune checkpoint inhibitors approved are monoclonal antibodies restricted to molecules on T cells and are widely used in the clinic for the treatment of cancer patients. Neutrophils are the most abundant immune cell population in the circulation and, together with macrophages, are present in the microenvironment of many cancer types, however they are mainly suppressive immune cells and their existence is often associated with cancer progression. Targeting myeloid cells by reversing their immunosuppressive features may be beneficial. Upregulation of surface sialic acid on cancer cells activates sialic acid-binding immunoglobulin-type lectin (Siglec) inhibitory receptors on immune cells and prevents an immune response against tumor cells. This study investigates the role of sialic acid in the regulation of antibody-dependent myeloid cell activation against cancer cells. The presence of sialic acid turned out to inhibit antibody-dependent cellular phagocytosis by human macrophages (ADCP) and to diminish antibody-dependent cellular cytotoxicity mediated by human neutrophils (ADCC). Importantly, Siglec-9 could be identified as a key player in antibody-mediated cytotoxic activity of neutrophils with the application of a Siglec-9 blocking antibody. Additionally, bispecific antibody-lectin proteins that combine a cancer targeting Fab with a Siglec decoy receptor through an Fc part, were evaluated as potential and promising therapeutic tools to enhance neutrophil cytotoxicity against cancer cells. Taken together, it could be shown that the sialic acid/Siglec axis regulates antibody-dependent cytotoxic activity of myeloid cells and that it is a promising immune checkpoint to target that opens new perspectives in cancer immunotherapy

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Klaas, M., Dubock, S., Ferguson, D. J. P., & Crocker, P. R. (2023). Sialoadhesin (CD169/Siglec-1) is an extended molecule that escapes inhibitory cis-interactions and synergizes with other macrophage receptors to promote phagocytosis. Glycoconjugate Journal, 40(2), 213–223.

MLA Style

Klaas, M, et al. “Sialoadhesin (CD169/Siglec-1) Is an Extended Molecule That Escapes Inhibitory Cis-Interactions and Synergizes with Other Macrophage Receptors to Promote Phagocytosis.” Glycoconjugate Journal, vol. 40, no. 2, 2023, pp. 213–23.

Chicago Style

Klaas, M, S Dubock, DJP Ferguson, and PR Crocker. 2023. “Sialoadhesin (CD169/Siglec-1) Is an Extended Molecule That Escapes Inhibitory Cis-Interactions and Synergizes with Other Macrophage Receptors to Promote Phagocytosis.” Glycoconjugate Journal 40 (2): 213–23.
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