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Author Spotlight: Dendritic Cells Maturation Using Sialidases-Based Enzymatic Treatment of the Cell Surface
Published on: October 20, 2023
The functional role of L-fucose on dendritic cell function and polarization
Chase Burton1,2,3, Amirreza Bitaraf2,4,5, Kara Snyder4,5,6
1Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States.
Abstract:
Despite significant advances in the development and refinement of immunotherapies administered to combat cancer over the past decades, a number of barriers continue to limit their efficacy. One significant clinical barrier is the inability to mount initial immune responses towards the tumor. As dendritic cells are central initiators of immune responses in the body, the elucidation of mechanisms that can be therapeutically leveraged to enhance their functions to drive anti-tumor immune responses is urgently needed. Here, we report that the dietary sugar L-fucose can be used to enhance the immunostimulatory activity of dendritic cells (DCs). L-fucose polarizes immature myeloid cells towards specific DC subsets, specifically cDC1 and moDC subsets. In vitro, L-fucose treatment enhances antigen uptake and processing of DCs. Furthermore, our data suggests that L-fucose-treated DCs increase stimulation of T cell populations. Consistent with our functional assays, single-cell RNA sequencing of intratumoral DCs from melanoma- and breast tumor-bearing mice confirmed transcriptional regulation and antigen processing as pathways that are significantly altered by dietary L-fucose. Together, this study provides the first evidence of the ability of L-fucose to bolster DC functionality and provides rational to further investigate how L-fucose can be used to leverage DC function in order to enhance current immunotherapy.
Insights
Dietary L-fucose enhances dendritic cell (DC) function, boosting anti-tumor immunity. This sugar promotes DC maturation and T cell stimulation, offering a novel strategy to improve cancer immunotherapy effectiveness.
Area of Science:
- Immunology
- Oncology
- Metabolic pathways
Background:
- Cancer immunotherapies face efficacy barriers, notably the failure to initiate anti-tumor immune responses.
- Dendritic cells (DCs) are critical initiators of immune responses, making their enhancement a key therapeutic goal.
Purpose of the Study:
- To investigate the potential of the dietary sugar L-fucose to enhance dendritic cell (DC) immunostimulatory activity.
- To explore L-fucose's mechanisms for improving DC function in the context of anti-tumor immunity.
Main Methods:
- In vitro analysis of L-fucose's effect on myeloid cell polarization and DC function, including antigen uptake and processing.
- Assessment of L-fucose-treated DC stimulation of T cell populations.
- Single-cell RNA sequencing of intratumoral DCs in tumor-bearing mice to identify molecular pathways affected by L-fucose.
Main Results:
- L-fucose treatment polarized immature myeloid cells towards specific DC subsets (cDC1 and moDC).
- In vitro, L-fucose enhanced DC antigen uptake, processing, and subsequent T cell stimulation.
- Single-cell RNA sequencing confirmed that dietary L-fucose significantly altered transcriptional regulation and antigen processing pathways in intratumoral DCs.
Conclusions:
- L-fucose demonstrates the ability to bolster DC functionality, enhancing their capacity to initiate anti-tumor immune responses.
- This study provides a rationale for investigating L-fucose as a therapeutic agent to augment DC function and improve cancer immunotherapy outcomes.
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