Targeting glycans for cancer immunotherapy

1. Smith, B. A. H. & Bertozzi, C. R. The clinical impact of glycobiology: targeting selectins, Siglecs and mammalian glycans. Nat. Rev. Drug Discov. 20, 217–243 (2021). A review article that summarizes previous approaches to therapeutically target glycans and further highlights the roles of Siglecs and dysregulated glycosylation in cancer.

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2. Mei, Y. et al. Siglec-9 acts as an immune-checkpoint molecule on macrophages in glioblastoma, restricting T-cell priming and immunotherapy response. Nat. Cancer 4, 1273–1291 (2023). This paper identified the Siglec-9–sialic acid axis as an immune checkpoint in glioblastoma and a potential mechanism of resistance to PD-1 blockade in humans.

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3. Ibarlucea-Benitez, I., Weitzenfeld, P., Smith, P. & Ravetch, J. V. Siglecs-7/9 function as inhibitory immune checkpoints in vivo and can be targeted to enhance therapeutic antitumor immunity. Proc. Natl Acad. Sci. USA 118, e2107424118 (2021). This paper used humanized animal models of cancer to show that knocking out Siglec-7 and Siglec-9 augments the efficacy of checkpoint inhibitors and Siglec-7/9-blocking antibodies enhance antitumor immune responses.

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4. Theruvath, J. et al. Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication. Nat. Med. 28, 333–344 (2022). This paper showed that Siglec-7 and CD47 are distinct axes of immune suppression in cancer and that blockade of both Siglec-7 and CD47 improved immune control of cancer.

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This is a summary of: Stark, J. C. et al. Antibody-lectin chimeras for glyco-immune checkpoint blockade. Nat. Biotechnol. https://doi.org/10.1038/s41587-025-02884-6 (2025).