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Review
. 2022 Jun 4;10(6):2366-2382.
doi: 10.1016/j.gendis.2022.05.020. eCollection 2023 Nov.

A new emerging target in cancer immunotherapy: Galectin-9 (LGALS9)

Yan Lv  1 , Xiao Ma  2 , Yuxin Ma  1 , Yuxin Du  1 , Jifeng Feng  1
Affiliations
Review

A new emerging target in cancer immunotherapy: Galectin-9 (LGALS9)

Yan Lv et al. Genes Dis. .

Abstract

Over the past few decades, advances in immunological knowledge have led to the identification of novel immune checkpoints, reinvigorating cancer immunotherapy. Immunotherapy, represented by immune checkpoint inhibitors, has become the leader in the precision treatment of cancer, bringing a new dawn to the treatment of most cancer patients. Galectin-9 (LGALS9), a member of the galectin family, is a widely expressed protein involved in immune regulation and tumor pathogenesis, and affects the prognosis of various types of cancer. Galectin-9 regulates immune homeostasis and tumor cell survival through its interaction with its receptor Tim-3. In the review, based on a brief description of the signaling mechanisms and immunomodulatory activities of galectin-9 and Tim-3, we summarize the targeted expression patterns of galectin-9 in a variety of malignancies and the promising mechanisms of anti-galectin-9 therapy in stimulating anti-tumor immune responses.

Keywords: Galectin-9; Immune checkpoint inhibitors; Immunotherapy; Monoclonal antibody; Tim-3.

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Figures

Fig. 1
Figure 1
Galectin family in mammals. Fifteen galectins have been described in mammals, 11 of which have also been found in humans (located in the light-colored area at the top of the diagram). This figure shows the structural variation and classification of different subtypes of galectins.
Fig. 2
Figure 2
The binding partners of Gal-9. Gal-9 binds to multiple receptors on the cell surface. Binding of Gal-9 to Tim-3 induces T cell apoptosis under physiological conditions, and forms autocrine loop with Tim-3 under pathological conditions, leading to reduced immune surveillance and promoting disease progression. PD-1 binding to Gal-9 plays a key role in inhibiting anti-tumor response and promoting T cell death.
Fig. 3
Figure 3
Different expression of Gal-9 in various types of human cancers. Gal-9 expression can be abnormally up-regulated or down-regulated during tumor-genesis to promote or inhibit tumor progression. Red arrow: Gal-9 increases with tumor progression. Blue arrow: Gal-9 decrease during tumorigenesis.
See this image and copyright information in PMC

References

    1. Cooper D.N. Galectinomics: finding themes in complexity. Biochim Biophys Acta. 2002;1572(2–3):209–231. - PubMed
    1. Méndez-Huergo S.P., Blidner A.G., Rabinovich G.A. Galectins: emerging regulatory checkpoints linking tumor immunity and angiogenesis. Curr Opin Immunol. 2017;45:8–15. - PubMed
    1. Vasta G.R. Galectins in host-pathogen interactions: structural, functional and evolutionary aspects. Adv Exp Med Biol. 2020;1204:169–196. - PubMed
    1. Ahmad N., Gabius H.J., André S., et al. Galectin-3 precipitates as a pentamer with synthetic multivalent carbohydrates and forms heterogeneous cross-linked complexes. J Biol Chem. 2004;279(12):10841–10847. - PubMed
    1. Yang R.Y., Rabinovich G.A., Liu F.T. Galectins: structure, function and therapeutic potential. Expet Rev Mol Med. 2008;10:e17. - PubMed