Current state-of-the-art on ganglioside-mediated immune modulation in the tumor microenvironment

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.

Automated summary

Gangliosides are sialylated glycolipids that play a crucial role in cellular signaling. Changes in their composition during malignant transformation are associated with negative effects on patient survival. Gangliosides released by cancer cells in the tumor microenvironment have immunosuppressive activities and promote tumor progression. Understanding the role of gangliosides in immunomodulation and their potential as therapeutic targets is important for future immunotherapy regimens.