Sialylation-dependent interaction between PD-L1 and CD169 promotes monocyte adhesion to endothelial cells

Cai, Kebo; Chen, Qihang; Shi, Danfang; Huang, Sijing; Ai, Zhilong; Jiang, Jianhai

doi:10.1093/glycob/cwad005

Cited by 3 publications

(1 citation statement)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD169, a member of the Siglec family, is expressed on the surfaces of specific subsets of macrophages, precursor monocytes and DCs. It contributes to cell-cell adhesion and cell-pathogen interactions since it has high affinity for α2 3 glycosyltransferase and glucosidase and communicates with other immune cells by binding to other cell-surface polysaccharides (e.g., CD43 on T cells) [42,43]. The expression of CD169 is induced on monocytes upon stimulation via type I INF pathways [14] and is associated with higher co-expression levels of co-stimulatory and HLA molecules, suggesting an increased activation state [44].…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of CD169 on Monocytes in Adult-Onset Kikuchi–Fujimoto Disease

Malipiero,

Machin,

Ermacora

et al. 2023

Hemato

View full text Add to dashboard Cite

Kikuchi–Fujimoto disease (KFD) is a rare, benign lymphoproliferative disease of uncertain origin that can mimic other inflammatory or clonal lymphoproliferative disorders. Given the lack of available blood biomarkers, diagnosis is based on the biopsy of an affected lymph node. In recent years, evidence has been mounting that a dysregulated type I INF innate immune response plays a pivotal role in the pathogenesis of the disease and might be a future therapeutic target. Nonetheless, laboratory assays measuring the expression of interferon alpha (INFα) and INF-stimulated genes (ISGs) are cumbersome and not widely available, limiting their use in clinical and translational research and encouraging the use of more convenient surrogate markers. In this study, a rapid flow cytometry assay detected increased levels of expression of CD169 (Siglec-1), an INFα-induced surface protein involved in innate immunity regulation, on circulating monocytes from two patients with KFD. Our results are in line with previous experiences and set the stage for a more extended investigation into the use of this assay in exploring the pathophysiology of KFD.

show abstract

Section: Discussionmentioning

confidence: 99%

Increased Expression of CD169 on Monocytes in Adult-Onset Kikuchi–Fujimoto Disease

Malipiero,

Machin,

Ermacora

et al. 2023

Hemato

View full text Add to dashboard Cite

show abstract

Personalised medicine in juvenile dermatomyositis: From novel insights in disease mechanisms to changes in clinical practice

Veldkamp,

van Wijk,

van Royen-Kerkhof

et al. 2024

Best Practice & Research Clinical Rheumatology

View full text Add to dashboard Cite

Targeting Tumor-Associated Sialic Acids Using Chimeric Switch Receptors Based on Siglec-9 Enhances the Antitumor Efficacy of Engineered T Cells

Eisenberg,

Hoogi,

Katzman

et al. 2024

Cancer Immunology Research

View full text Add to dashboard Cite

Cancer exploits different mechanisms to escape T-cell immunosurveillance, including overexpression of checkpoint ligands, secretion of immunosuppressive molecules, and aberrant glycosylation. Herein, we report that IFNγ, a potent immunomodulator secreted in the tumor microenvironment, can induce α2,6 hypersialylation in cancer cell lines derived from various histologies. We then focused on Siglec-9, a receptor for sialic acid moieties, and demonstrated that the Siglec-9+ T-cell population displayed reduced effector function. We speculated that Siglec-9 in primary human T cells can act as a checkpoint molecule and demonstrated that knocking out Siglec-9 using a CRISPR/Cas9 system enhanced the functionality of primary human T cells. Finally, we aimed to augment cancer-specific T-cell activity by taking advantage of tumor hypersialylation. Thus, we designed several Siglec-9–based chimeric switch receptors (CSRs), which included an intracellular moiety derived from costimulatory molecules (CD28/41BB) and different hinge regions. In an antigen specific context, T cells transduced with Siglec-9 CSRs demonstrated increased cytokine secretions and upregulation of activation markers. Moreover, T cells equipped with specific Siglec-9 CSRs mediated robust antitumor activity in a xenograft model of human tumors. Overall, this work sheds light on tumor evasion mechanisms mediated by sialylated residues and exemplifies an approach to improve engineered T cell–based cancer treatment.

show abstract

Sialylation-dependent interaction between PD-L1 and CD169 promotes monocyte adhesion to endothelial cells

Cited by 3 publications

References 58 publications

Increased Expression of CD169 on Monocytes in Adult-Onset Kikuchi–Fujimoto Disease

Increased Expression of CD169 on Monocytes in Adult-Onset Kikuchi–Fujimoto Disease

Personalised medicine in juvenile dermatomyositis: From novel insights in disease mechanisms to changes in clinical practice

Targeting Tumor-Associated Sialic Acids Using Chimeric Switch Receptors Based on Siglec-9 Enhances the Antitumor Efficacy of Engineered T Cells

Contact Info

Product

Resources

About