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Review | Open Access

Recent progress in targeting the sialylated glycan-SIGLEC axis in cancer immunotherapy

Department of General Surgery of Ruijin Hospital, Shanghai Institute of Digestive Surgery, and Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China
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Abstract

Malignant tumors are complex structures composed of cancer cells and tumor microenvironmental cells. In this complex structure, cells cross-talk and interact, thus jointly promoting cancer development and metastasis. Recently, immunoregulatory molecule-based cancer immunotherapy has greatly improved treatment efficacy for solid cancers, thus enabling some patients to achieve persistent responses or cure. However, owing to the development of drug-resistance and the low response rate, immunotherapy against the available targets PD-1/PD-L1 or CTLA-4 has limited benefits. Although combination therapies have been proposed to enhance the response rate, severe adverse effects are observed. Thus, alternative immune checkpoints must be identified. The SIGLECs are a family of immunoregulatory receptors (known as glyco-immune checkpoints) discovered in recent years. This review systematically describes the molecular characteristics of the SIGLECs, and discusses recent progress in areas including synthetic ligands, monoclonal antibody inhibitors, and Chimeric antigen receptor T (CAR-T) cells, with a focus on available strategies for blocking the sialylated glycan-SIGLEC axis. Targeting glyco-immune checkpoints can expand the scope of immune checkpoints and provide multiple options for new drug development.

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Cancer Biology & Medicine
Pages 369-384
Cite this article:
Yu Y, Peng W. Recent progress in targeting the sialylated glycan-SIGLEC axis in cancer immunotherapy. Cancer Biology & Medicine, 2023, 20(5): 369-384. https://doi.org/10.20892/j.issn.2095-3941.2023.0046

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Received: 09 February 2023
Accepted: 27 March 2023
Published: 05 June 2023
©2023 Cancer Biology & Medicine.

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