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Updated: Feb 17, 2026
Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy
Published on: August 1, 2013
CD11c-targeted Delivery of DNA to Dendritic Cells Leads to cGAS- and STING-dependent Maturation
Marlene F Laursen1, Esben Christensen1, Laura L T Degn1
1Department of Health Science and Technology, Aalborg University.
Abstract:
Immunotherapeutic activation of tumor-specific T cells has proven to be an interesting approach in anticancer treatment. Particularly, anti-CTLA-4 and anti-PD-1/PD-L1 treatment looks promising, and conceivably, even better clinical results might be obtained if such treatment could be combined with boosting the existing tumor-specific T-cell response. One way to achieve this could be by increasing the level of maturation of dendritic cells locally and in the draining lymph nodes. When exposed to cancer cells, dendritic cells may spontaneously mature because of danger-associated molecular patterns derived from the tumor cells. Double-stranded DNA play a particularly important role in the activation of the dendritic cells, through engagement of intracellular DNA-sensors, and signaling through the adaptor protein STING. In the present study, we have investigated the maturational response of human monocyte-derived dendritic cells (moDC) and human monocytic THP-1 cells to targeted and untargeted DNA. We used an anti-CD11c antibody conjugated with double-stranded DNA to analyze the maturation status of human moDCs, as well as maturation using a cGAS KO and STING KO THP-1 cell maturation model. We found that dendritic cells can mature after exposure to cytoplasmic double-stranded DNA delivered through CD11c-mediated endocytosis. Moreover, we show that THP-1 cells matured using IL-4, GM-CSF, and ionomycin upregulate DC-maturation markers after CD11c-targeted delivery of double-stranded DNA. This upregulation is completely abrogated in cGAS KO and STING KO cells.
Insights
Targeted delivery of double-stranded DNA enhances dendritic cell maturation, a key step for boosting anti-cancer T-cell responses. This approach shows promise for improving immunotherapies like anti-CTLA-4 and anti-PD-1/PD-L1 treatments.
Area of Science:
- Immunology
- Cancer Biology
- Cellular Signaling
Background:
- Cancer immunotherapies like anti-CTLA-4 and anti-PD-1/PD-L1 treatments aim to activate tumor-specific T cells.
- Enhancing dendritic cell (DC) maturation is crucial for boosting existing anti-cancer T-cell responses.
- Dendritic cells can mature upon encountering danger signals, such as double-stranded DNA (dsDNA), from tumor cells, activating intracellular sensors like cGAS and STING.
Purpose of the Study:
- To investigate the maturational response of human monocyte-derived dendritic cells (moDCs) and THP-1 cells to targeted and untargeted DNA.
- To explore the role of CD11c-mediated endocytosis in delivering dsDNA to DCs for maturation.
- To analyze the involvement of cGAS and STING pathways in dsDNA-induced DC maturation.
Main Methods:
- Human moDCs and THP-1 cells were utilized to study DC maturation.
- An anti-CD11c antibody conjugated with dsDNA was used for targeted delivery.
- CRISPR-Cas9 gene editing was employed to create cGAS knockout (KO) and STING KO THP-1 cell lines to assess pathway-specific contributions.
Main Results:
- Dendritic cells undergo maturation upon exposure to cytoplasmic dsDNA delivered via CD11c-mediated endocytosis.
- Targeted delivery of dsDNA to THP-1 cells, pre-matured with IL-4, GM-CSF, and ionomycin, upregulated DC-maturation markers.
- This dsDNA-induced upregulation of maturation markers was completely abolished in cGAS KO and STING KO THP-1 cells, confirming the critical role of this pathway.
Conclusions:
- Cytoplasmic dsDNA delivery through CD11c-mediated endocytosis effectively matures dendritic cells.
- The cGAS-STING signaling pathway is essential for dsDNA-induced dendritic cell maturation.
- Targeted delivery of dsDNA represents a potential strategy to enhance DC maturation for improved cancer immunotherapy.
