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Updated: Mar 20, 2026
Author Spotlight: Dendritic Cells Maturation Using Sialidases-Based Enzymatic Treatment of the Cell Surface
Published on: October 20, 2023
Sialic acid removal from dendritic cells improves antigen cross-presentation and boosts anti-tumor immune responses
Mariana Silva1, Zélia Silva1,2, Graça Marques1
1CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.
Abstract:
Dendritic cells (DCs) hold promise for anti-cancer immunotherapy. However, clinically, their efficiency is limited and novel strategies to improve DC-mediated anti-tumor responses are needed. Human DCs display high content of sialic acids, which inhibits their maturation and co-stimulation capacity. Here, we aimed to understand whether exogenous desialylation of DCs improves their anti-tumor immunity. Compared to fully sialylated DCs, desialylated human DCs loaded with tumor-antigens showed enhanced ability to induce autologous T cells to proliferate, to secrete Th1 cytokines, and to specifically induce tumor cell apoptosis. Desialylated DCs showed an increased expression of MHC-I and -II, co-stimulatory molecules and an augmented secretion of IL-12. Desialylated HLA-A*02:01 DCs pulsed with gp100 peptides displayed enhanced peptide presentation through MHC-I, resulting in higher activation ofgp100280-288 specific CD8+ cytotoxic T cells. Desialylated murine DCs also exhibited increased MHC and co-stimulatory molecules and higher antigen cross-presentation via MHC-I. These DCs showed higher ability to activate antigen-specific CD4+ and CD8+ T cells, and to specifically induce tumor cell apoptosis. Collectively, our data demonstrates that desialylation improves DCs' ability to elicit T cell-mediated anti-tumor activity, due to increased MHC-I expression and higher antigen presentation via MHC-I. Sialidase treatment of DCs may represent a technology to improve the efficacy of antigen loaded-DC-based vaccines for anti-cancer immunotherapy.
Insights
Removing sialic acids from dendritic cells (DCs) enhances their ability to fight cancer. This desialylation improves T cell activation and anti-tumor immunity, offering a new strategy for cancer immunotherapy.
Area of Science:
- Immunology
- Cancer Research
- Biotechnology
Background:
- Dendritic cells (DCs) are crucial for anti-cancer immunotherapy but face limitations in clinical efficacy.
- High sialic acid content on human DCs can impede their maturation and co-stimulatory functions, reducing anti-tumor responses.
- Novel strategies are needed to enhance DC-mediated anti-tumor immunity.
Purpose of the Study:
- To investigate if exogenous desialylation of dendritic cells (DCs) can improve their anti-tumor immunity.
- To evaluate the impact of desialylation on DC maturation, antigen presentation, and T cell activation.
Main Methods:
- Human and murine dendritic cells (DCs) were treated with sialidase to remove sialic acids (desialylation).
- Desialylated DCs were loaded with tumor antigens or peptides.
- The expression of MHC and co-stimulatory molecules, cytokine secretion, and T cell activation (proliferation, cytokine secretion, cytotoxicity) were analyzed.
- Antigen presentation via MHC-I was assessed using specific peptides and T cell lines.
Main Results:
- Desialylated DCs exhibited enhanced expression of MHC-I, MHC-II, and co-stimulatory molecules.
- Desialylation augmented the secretion of IL-12 and improved antigen presentation via MHC-I.
- Desialylated DCs demonstrated superior ability to induce autologous T cell proliferation, Th1 cytokine secretion, tumor-specific cytotoxic T cell activation, and tumor cell apoptosis.
Conclusions:
- Exogenous desialylation significantly enhances the capacity of dendritic cells (DCs) to elicit T cell-mediated anti-tumor activity.
- Improved MHC-I expression and antigen presentation are key mechanisms underlying the enhanced anti-tumor immunity induced by desialylated DCs.
- Sialidase treatment of DCs represents a promising technological approach to improve the efficacy of DC-based vaccines for cancer immunotherapy.
