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

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.

Multi-dimensional role of gangliosides in modulating cancer hallmarks and their prospects in targeted cancer therapy

“…Treatment with anti GD2 antibody was also shown to sensitise human cancer cells to macrophage mediated phagocytosis by blocking siglec-7 binding ( Theruvath et al, 2022 ), clearly suggesting the role of GD2 in Siglec-7 mediated immune evasion in cancer. Siglec-1 on the other hand was known to be expressed in human macrophages and interacts with GM3, GD1a, GD1b, GT1b resulting in phagocytosis ( van der Haar Àvila et al, 2023 ). Taken together, these findings have solidified the importance of tumor shed gangliosides in helping cancer cells to evade and escape the host immune response, thereby promoting survival, growth, and overall progression of the disease.…”

Microbiome–Metabolomic Analysis Revealed the Immunoprotective Effects of the Extract of Vanilla planifolia Andrew (EVPA) on Immunosuppressed Mice

“…Ceramide is considered a key factor in mediating and regulating the functions of various immune cells, such as modulating immune cell responses to bacteria, viruses, and other foreign pathogens as well as the production of cytokines [ 36 ]. GD1a (d18:1/22:0), a ganglioside, is a component of the cellular membrane that plays a crucial role in the regulation of cell signal transduction [ 37 ]. The levels of Cer (d18:1/18:0) and GD1a (d18:1/22:0) significantly increased in mice with immunosuppression induced by Cy, and EVPA treatment restored this disruption.…”

Synergistic effects of immune checkpoints and checkpoint inhibitors in inflammatory neuropathies: Implications and mechanisms

“…Gangliosides can be considered as additional immune checkpoint molecules in systemic malignancies as they contribute to T cell dysfunction and thus allow tumor cells to evade the immune response. 88 Besides this, gangliosides expressed on the nerve cells have the potential to induce neuroinflammation and contribute to T A B L E 1 Case reports of inflammatory neuropathies in patients receiving immune checkpoint inhibitors.…”