Demethylation of cancer/testis antigens and CpG ODN stimulation enhance dendritic cell and cytotoxic T lymphocyte function in a mouse mammary model

癌症/睾丸抗原的去甲基化和 CpG ODN 刺激增强小鼠乳腺模型中的树突状细胞和细胞毒性 T 淋巴细胞功能

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作者:Jun-Zhong Sun, Lei Gao, Li Gao, Wei Wang, Nan Du, Juan Yang, Ling Wan, Fang Liu, Li-li Wang, Li Yu

Background

Cancer/testis antigens (CTAs) are ideal targets for cancer immunotherapy in virtue of their restricted expression profile in normal tissues. However, CTA-targeted immunotherapy has been rather disappointing clinical setting for CTAs are downregulated by cytosine-phosphate-guanosine (CpG) methylation in their promoter regions, so that tumor cells have low immunogenicity.

Conclusions

Our results suggested that CTA induction and immune adjuvant stimulation is a feasible strategy in cancer immunotherapy.

Methods

We reinduced mouse CTA P1A through demethylation process and generated P1A-specific cytotoxic lymphocytes (CTLs) by immunizing BALB/c (H-2(d)) mice with dendritic cells pulsed with a P1A-specific peptide and CpG oligodeoxynucleotide (ODN) immune adjuvant.

Results

We found that demethylation and CpG ODN immune adjuvant stimulation facilitated DC maturation and enhanced the allogenic capacity of P1A-specific CTLs against target cells both in vitro and in vivo. Conclusions: Our results suggested that CTA induction and immune adjuvant stimulation is a feasible strategy in cancer immunotherapy.

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