Immune Response Modulation by Tumor-Secreted Glycosphingolipids

Lardone, Ricardo Dante; Cely, Ingrid; Sieling, Peter A.; Lee, Delphine J.

doi:10.4172/2168-958x.1000107

Cited by 2 publications

(2 citation statements)

References 139 publications

(97 reference statements)

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“…Thus, in addition to cell internalization, sorting to lysosomes or plasma membrane recycling, gangliosides can be actively shed from the membrane of one cell and taken up by other cells by insertion of their lipid anchors into the cell membrane. Although the shedding and uptake of gangliosides are a physiological process observed in many types of cells, increased levels have been detected in various tumors, such as melanomas, renal carcinoma, astrocytomas, and glioblastomas ( 35 – 39 ). Many reports have described that shedding of gangliosides helps to suppress the immune response, probably by modifying membrane composition of immune cells and, hence, inhibiting their function and allowing tumor escape.…”

Section: Glycolipid Metabolism and Functionsmentioning

confidence: 99%

“…At this respect, N -butyldeoxynojirimycin, an imino-sugar administered orally to inhibit GlcCer synthase, delayed tumor development of MEB4 murine cells ( 146 ). This could be further explored in human cancer as a therapeutic approach, aiming at intervene on GSL metabolism of tumor cells and modulate GSLs shedding, thus lessening the immunomodulatory effects of GSLs ( 39 ).…”

Section: Immunotherapies Using Gangliosides As Molecular Targetsmentioning

confidence: 99%

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Dysregulated Expression of Glycolipids in Tumor Cells: From Negative Modulator of Anti-tumor Immunity to Promising Targets for Developing Therapeutic Agents

2016

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Glycolipids are complex molecules consisting of a ceramide lipid moiety linked to a glycan chain of variable length and structure. Among these are found the gangliosides, which are sialylated glycolipids ubiquitously distributed on the outer layer of vertebrate plasma membranes. Changes in the expression of certain species of gangliosides have been described to occur during cell proliferation, differentiation, and ontogenesis. However, the aberrant and elevated expression of gangliosides has been also observed in different types of cancer cells, thereby promoting tumor survival. Moreover, gangliosides are actively released from the membrane of tumor cells, having a strong impact on impairing anti-tumor immunity. Beyond the undesirable effects of gangliosides in cancer cells, a substantial number of cancer immunotherapies have been developed in recent years that have used gangliosides as the main target. This has resulted in successful immune cell- or antibody-responses against glycolipids, with promising results having been obtained in clinical trials. In this review, we provide a general overview on the metabolism of glycolipids, both in normal and tumor cells, as well as examining glycolipid-mediated immune modulation and the main successes achieved in immunotherapies using gangliosides as molecular targets.

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Section: Glycolipid Metabolism and Functionsmentioning

confidence: 99%

Section: Immunotherapies Using Gangliosides As Molecular Targetsmentioning

confidence: 99%

Dysregulated Expression of Glycolipids in Tumor Cells: From Negative Modulator of Anti-tumor Immunity to Promising Targets for Developing Therapeutic Agents

2016

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Neolactotetraosylceramide: A novel non-invasive urinary biomarker for bladder cancer

Moreira,

Rossdam,

Beimdiek

et al. 2023

Preprint

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There is an urgent need to identify noninvasive biomarkers for bladder cancer. Here, we applied glycan analytics by multiplex capillary gel electrophoresis coupled to laser-induced fluorescence detection (xCGE-LIF) to unravel the global glycosphingolipid (GSL)-glycan profile of primary tumor tissues and urine samples from bladder cancer patients. Thereby, we detected neolactotetraosylceramide (Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc-Cer, nLc4) at significantly increased levels from tumorigenic regions of bladder tissues compared to non-malignant adjacent material (n = 30). Specific expression of nLc4 in cancer tissue was confirmed by immunofluorescence staining. GSL-glycan profiling by xCGE-LIF of urinary exosomes showed that nLc4 is increased in bladder cancer patients (n = 16) when compared to controls (n = 50), with an overall sensitivity of 57% and specificity of 90%. We set-up an ELISA targeting nLc4-containing urinary exosomes from bladder cancer patients (n = 9) and cancer-free individuals (n = 9) demonstrating an overall sensitivity and specificity of 89% and 78%, respectively.

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Immune Response Modulation by Tumor-Secreted Glycosphingolipids

Cited by 2 publications

References 139 publications

Dysregulated Expression of Glycolipids in Tumor Cells: From Negative Modulator of Anti-tumor Immunity to Promising Targets for Developing Therapeutic Agents

Dysregulated Expression of Glycolipids in Tumor Cells: From Negative Modulator of Anti-tumor Immunity to Promising Targets for Developing Therapeutic Agents

Neolactotetraosylceramide: A novel non-invasive urinary biomarker for bladder cancer

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