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Updated: Aug 24, 2026
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Nitric oxide confers therapeutic activity to dendritic cells in a mouse model of melanoma
Cristiana Perrotta1, Sestina Falcone, Annalisa Capobianco
1Department of Pharmaco-Biology, University of Calabria, Rende.
Abstract:
Susceptibility of dendritic cells (DCs) to tumor-induced apoptosis reduces their efficacy in cancer therapy. Here we show that delivery within exponentially growing B16 melanomas of DCs treated ex vivo with nitric oxide (NO), released by the NO donor (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO), significantly reduced tumor growth, with cure of 37% of animals. DETA-NO-treated DCs became resistant to tumor-induced apoptosis because DETA-NO prevented tumor-induced changes in the expression of Bcl-2, Bax, and Bcl-xL; activation of caspase-9; and a reduction in the mitochondrial membrane potential. DETA-NO also increased DC cytotoxic activity against tumor cells and DC ability to trigger T-lymphocyte proliferation. All of the effects of DETA-NO were mediated through cGMP generation. NO and NO-generating drugs may therefore be used to increase the anticancer efficacy of DCs.
Insights
Nitric oxide (NO) treatment enhances dendritic cell (DC) resistance to tumor-induced apoptosis, improving cancer therapy. This approach significantly reduced tumor growth and increased DC anti-tumor activity.
Area of Science:
- Immunology
- Cancer Biology
- Pharmacology
Background:
- Dendritic cells (DCs) are crucial for anti-tumor immunity.
- Tumor-induced apoptosis diminishes DC efficacy in cancer therapy.
- Novel strategies are needed to enhance DC function in cancer treatment.
Purpose of the Study:
- To investigate the effect of nitric oxide (NO) on DC apoptosis and anti-tumor activity.
- To determine if NO-treated DCs can improve cancer therapy outcomes.
- To elucidate the mechanisms underlying NO's protective effects on DCs.
Main Methods:
- DCs were treated ex vivo with a nitric oxide donor, DETA-NO.
- Treated DCs were delivered into B16 melanomas in a mouse model.
- Tumor growth, DC apoptosis markers (Bcl-2, Bax, Bcl-xL, caspase-9, mitochondrial membrane potential), cytotoxic activity, and T-lymphocyte proliferation were assessed.
- cGMP levels were measured to confirm NO signaling pathways.
Main Results:
- DETA-NO treatment rendered DCs resistant to tumor-induced apoptosis.
- NO prevented changes in apoptosis-related proteins and mitochondrial function.
- DETA-NO-treated DCs exhibited enhanced cytotoxic activity against tumor cells.
- NO-treated DCs significantly increased T-lymphocyte proliferation.
- Tumor growth was significantly reduced, with a 37% cure rate in treated animals.
- All observed effects were mediated by cGMP generation.
Conclusions:
- Ex vivo NO treatment of DCs enhances their resistance to tumor-induced apoptosis.
- NO-treated DCs demonstrate improved anti-tumor cytotoxicity and T-cell activation.
- NO-based strategies hold promise for improving DC-based cancer immunotherapy.
- Nitric oxide donors may represent a valuable tool to augment the anticancer efficacy of dendritic cells.
