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Current state-of-the-art on ganglioside-mediated immune modulation in the tumor microenvironment
Irene van der Haar Àvila1,2,3, Britt Windhouwer1, Sandra J van Vliet4,5,6
1Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan, 1117, Amsterdam, the Netherlands.
Abstract:
Gangliosides are sialylated glycolipids, mainly present at the cell surface membrane, involved in a variety of cellular signaling events. During malignant transformation, the composition of these glycosphingolipids is altered, leading to structural and functional changes, which are often negatively correlated to patient survival. Cancer cells have the ability to shed gangliosides into the tumor microenvironment, where they have a strong impact on anti-tumor immunity and promote tumor progression. Since most ganglioside species show prominent immunosuppressive activities, they might be considered checkpoint molecules released to counteract ongoing immunosurveillance. In this review, we highlight the current state-of-the-art on the ganglioside-mediated immunomodulation, specified for the different immune cells and individual gangliosides. In addition, we address the dual role that certain gangliosides play in the tumor microenvironment. Even though some ganglioside species have been more extensively studied than others, they are proven to contribute to the defense mechanisms of the tumor and should be regarded as promising therapeutic targets for inclusion in future immunotherapy regimens.
Insights
Cancer cells release gangliosides, which suppress anti-tumor immunity and promote tumor growth. These immunosuppressive molecules are promising targets for future cancer immunotherapy strategies.
Area of Science:
- Cancer Biology
- Immunology
- Glycobiology
Background:
- Gangliosides are sialylated glycolipids crucial for cell surface signaling.
- Malignant transformation alters ganglioside composition, impacting patient survival.
- Cancer cells shed gangliosides into the tumor microenvironment, influencing immunity and progression.
Purpose of the Study:
- To review the current understanding of ganglioside-mediated immunomodulation in cancer.
- To detail the effects of specific gangliosides on different immune cells.
- To explore the dual roles of gangliosides in the tumor microenvironment.
Main Methods:
- Literature review of studies on gangliosides and cancer immunology.
- Analysis of ganglioside structures and their immunosuppressive activities.
- Examination of ganglioside roles in tumor progression and immune evasion.
Main Results:
- Gangliosides exhibit potent immunosuppressive activities, acting as immune checkpoint molecules.
- Specific ganglioside species differentially modulate various immune cells.
- Gangliosides contribute significantly to tumor defense mechanisms and progression.
Conclusions:
- Gangliosides are key players in tumor-induced immunosuppression.
- Understanding individual ganglioside functions is vital for targeted therapies.
- Gangliosides represent promising therapeutic targets for enhancing immunotherapy efficacy.
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