The Immunomodulatory Role of Galectin-1 in the Tumour Microenvironment and Strategies for Therapeutic Applications
Simple Summary
Abstract
1. Introduction
2. Pathological Function of Gal1
3. The Immunomodulatory Role of Gal1 in the TME
3.1. Suppression of T Cell Function
3.2. Gal1-Induced Suppression by Regulatory T Cells
3.3. Gal1 Induced Modulation of Macrophages
3.4. Gal1 Inhibition Can Enhance the Efficacy of Existing Immunotherapies and Help Overcome Treatment Resistance
4. Gal1 as a Potential Therapeutic Target
4.1. Non-Carbohydrate Gal1 Inhibitors
4.2. OTX008—A Selective Gal1 Inhibitor
4.3. Anti-Gal1 Monoclonal Antibodies
4.4. Vaccinations Against Gal1
5. Future Perspective
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Cancer Type | Gal1 Upregulation Effects | Gal1 Targeting Outcomes | Refs |
---|---|---|---|
Melanoma | ↑ Tumour growth ↓ Th-1 anti-tumour response |
| [9,10] |
Breast | ↑ Aggression of human breast tumour ↑ Tumour growth and metastasis ↑ Frequency of Treg cells including: CD4+, CD25+ and Foxp3+ |
| [11,12] |
Epithelial Ovarian Cancer (high-grade serous carcinoma) | ↑ Cell proliferation ↑ Angiogenesis |
| [7,13] |
Non–small cell lung cancer | ↑ COX-2 expression and prostaglandin E2 to stimulate tumour progression ↑ Chemotherapy resistance ↑ Cell migration and invasion |
| [14] |
Castration-Resistant Prostate Cancer | ↑ Cell adhesion ↑ Cell migration ↑ Tumour invasion |
| [15] |
Urinary bladder urothelial carcinoma cell | ↑ Cell proliferation ↑ Tumour invasive capability ↑ Clonogenicity |
| [16] |
Follicular and papillary carcinomas | ↑ Cell proliferation ↑ Cell migration ↑ Invasion ↑ Tumour growth |
| [17] |
Pancreatic ductal adenocarcinoma | Induction of apoptosis of CD4+ and CD8+ T cells ↑ Th2 cytokine secretion from T cells ↑ Tumour growth |
| [18,19] |
Cutaneous head and neck cancer with perineural spread | ↑ T and B lymphocytes ↑ Fox-P3 expressing T cells Mediates tumour-host immune system interactions Creates an immune-privileged environment for tumour cells to evade host immunity |
| [20] |
Glioblastoma | ↑ Brain-infiltrating macrophages ↑ Myeloid-derived suppressor cells |
| [21] |
Neuroblastoma | Induced T cell apoptosis Inhibition of DC maturation |
| [22] |
Cancer Type | Agents | Theraputic Strategy/Modality | Development Stage | Materials | References |
---|---|---|---|---|---|
Melanoma | Thiodigalactoside | A small molecuale that inhibits Gal1 activity via binding to its CRD | Preclinical | Disaccharides | [67,68,69] |
4-F-GlcNAc | A metabolic inhibitor that disrupts the biosynthesis of LacNAc (N-acetyllactosamine), thereby reducing the availability of Gal1 binding sites on cell surface glycoproteins | Preclinical | Glycan | [70] | |
TRX–mGal1 | A recombinant vaccine protein was developed by fusing bacterial thioredoxin (Trx) with mouse Gal1 (mGal1) | Preclinical | Murine Gal1 vaccine | [71,72] | |
GM-CT-01 (Davanat) | It binds to Gal1, disrupting its interactions with glycosylated receptors on cell surfaces and hence modulating immune response | Clinical | Galactomannan | [73,74] | |
Ovarian | Anginex | Direct binding of the angiostatic agent to Gal1 alters its affinity for glycoproteins. Combatorial treatment with irofulven further reduce tumour growth. | Preclinical | β-peptide | [75,76,77,78] |
Non-small cell lung cancer | AP-74 M-545 | Designed to Specifically binds to Gal1, disrupting its interaction to glycosylated receptors | Preclinical | Single-stranded DNA aptamer | [70] |
Prostate carcinoma | LLS30 | An inhibitor that binds to CRD, preventing Gal1 binding to CD45 and leading to the suppression of T cells apoptosis. | Preclinical | Small molecule | [15,62] |
Kaposi sarcoma, prostate | 8F4F8G7 | Binding of the antibody to Gal1 inhibits Gal1-induced apoptosis of the activated T cells and cytotoxic T cells (CTL). | Preclinical | Monoclonal antibody | [79,80] |
Head-neck cancer | GR-MD-02 (Belapectin) | Inhibits extracellular Gal1 and Gal3 from interacting with the glycosylated receptor on tumour cells. | Phase I clinical trial | Polysaccharide | [5,81] |
Glioblastoma | Intranasal siRNA | The nanoparticles is capable of crossing the blood-brain barrier (BBB). Silencing Gal1 results in decreased tumour cell motility. | Preclinical | siRNA-loaded chitosan nanoparticles | [73,82,83] |
Neuroblastoma | Minigene DNA vaccine | The Gal1 DNA vaccine can trigger the antitumour cytotoxicity. | Preclinical | DNA plasmid | [84] |
Advanced solid tumours | OTX008 | A small molecule that selectively binds Gal1 and inhibits cell cycle prgression and enhances tumour cell cytotoxicity | Phase I clinical trial | Calixarene compound | [85,86,87,88] |
Metastatic colorectal cancer | GM-CT-01 (Davanat) | Treatment with GM-CT-01 observed an increase in IFN-γ secretion by T cells. | Phase II clinical trials | Polysaccharides | [74,89] |
Breast cancer | Thiodigalactoside | A small molecuale that inhibits Gal1 activity via binding to its CRD | Preclinical | Disaccharides | [69] |
Lymphoma | 4-F-GlcNAc | A metabolic inhibitor that disrupts the biosynthesis of LacNAc (N-acetyllactosamine), thereby reducing the availability of Gal1 binding sites on cell surface glycoproteins | Preclinical | Glycan | [70] |
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Griffiths, A.; Udomjarumanee, P.; Georgescu, A.-S.; Barri, M.; Zinovkin, D.A.; Pranjol, M.Z.I. The Immunomodulatory Role of Galectin-1 in the Tumour Microenvironment and Strategies for Therapeutic Applications. Cancers 2025, 17, 1888. https://doi.org/10.3390/cancers17111888
Griffiths A, Udomjarumanee P, Georgescu A-S, Barri M, Zinovkin DA, Pranjol MZI. The Immunomodulatory Role of Galectin-1 in the Tumour Microenvironment and Strategies for Therapeutic Applications. Cancers. 2025; 17(11):1888. https://doi.org/10.3390/cancers17111888
Chicago/Turabian StyleGriffiths, Alice, Palita Udomjarumanee, Andrei-Stefan Georgescu, Muruj Barri, Dmitry A. Zinovkin, and Md Zahidul I. Pranjol. 2025. "The Immunomodulatory Role of Galectin-1 in the Tumour Microenvironment and Strategies for Therapeutic Applications" Cancers 17, no. 11: 1888. https://doi.org/10.3390/cancers17111888
APA StyleGriffiths, A., Udomjarumanee, P., Georgescu, A.-S., Barri, M., Zinovkin, D. A., & Pranjol, M. Z. I. (2025). The Immunomodulatory Role of Galectin-1 in the Tumour Microenvironment and Strategies for Therapeutic Applications. Cancers, 17(11), 1888. https://doi.org/10.3390/cancers17111888