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[Antitumor effect of CpG oligonucleotides on human neuroblastoma xenografts in nude mice]
Qiang-Hua Yao1, Yan-Jing Tang, Feng-Hou Gao
1Department of Hematology/Oncology, Shanghai Children's Medical Center, The Third People's Hospital, Medical College of Shanghai Jiaotong University, Shanghai, 200127, PR China.
Background And Objective:
Synthetic CpG oligodeoxynucleotides(CpG ODN) containing unmethylated CpG dinucleotide motifs, which mimic the effects of bacterial DNA, can stimulate the host's immune defense to reject cancer cells as "non-self" signal. This study was to evaluate the antitumor effect of CpG ODN against human neuroblastoma xenografts in nude mice depending on the innate immunity.
Methods:
The cytotoxicity of CpG ODN on neuroblastoma SK-N-MC cells was detected by WST-1 assay in vitro. Neuroblastoma xenografts were built subcutaneously in nude mice. When palpable tumor developed, the mice were randomized into normal saline (NS), non-CpG ODN, and CpG ODN groups (each group contained six mice), and were administered every other day for two weeks. When tumor grew to 5 cm3, the mice were killed to observe tumor morphology by histology and histochemistry.
Results:
CpG ODN had no cytotoxicity on SK-N-MC cells in vitro. Tumor volume was significantly smaller in CpG ODN group than in NS and non-CpG ODN groups at the end of the observation [(0.14+/-0.03) cm3 vs. (2.97+/-0.40) cm3 and (3.80+/-1.12) cm3, P<0.01]. On HE-stained sections, the tumor tissues of CpG ODN group showed intratumoral infiltration of inflammatory cells and large areas of necrosis, whereas those of controls showed less infiltration and no necrosis. By immunohistochemistry, the tumor tissues of CpG ODN group showed more natural killer (NK) cells and macrophages as compared with those of control groups.
Conclusion:
CpG ODN may have therapeutic effect on neuroblastoma in nude mice via mediating the activity of NK cells and macrophages.
Insights
Synthetic CpG oligodeoxynucleotides (CpG ODN) demonstrated significant antitumor effects against neuroblastoma xenografts in mice by activating innate immunity. This immunotherapy approach enhanced natural killer cell and macrophage activity, leading to reduced tumor volume and necrosis.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Context:
- Synthetic CpG oligodeoxynucleotides (CpG ODN) mimic bacterial DNA to stimulate immune responses.
- Neuroblastoma is a pediatric cancer with limited treatment options.
- Innate immunity plays a crucial role in cancer surveillance and elimination.
Purpose:
- To evaluate the antitumor efficacy of CpG ODN in a human neuroblastoma xenograft model in nude mice.
- To investigate the role of innate immunity, specifically natural killer (NK) cells and macrophages, in mediating the effects of CpG ODN.
- To assess the direct cytotoxicity of CpG ODN on neuroblastoma cells in vitro.
Summary:
- CpG ODN exhibited no direct cytotoxicity against SK-N-MC neuroblastoma cells in vitro.
- In vivo, CpG ODN treatment significantly reduced tumor volume in neuroblastoma xenografts compared to control groups.
- Histological analysis revealed increased inflammatory cell infiltration and necrosis in tumors treated with CpG ODN.
Impact:
- CpG ODN demonstrates therapeutic potential for neuroblastoma by harnessing the host's innate immune system.
- The study highlights the importance of NK cells and macrophages in mediating CpG ODN's antitumor activity.
- This research may pave the way for novel immunotherapeutic strategies against neuroblastoma.
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