一种Toll样受体9（TLR9）激动剂通过不同机制增强肽和脂肽疫苗的抗肿瘤免疫力。

A TLR9 agonist enhances the anti-tumor immunity of peptide and lipopeptide vaccines via different mechanisms.

作者信息

Song Ying-Chyi, Liu Shih-Jen

机构信息

1] National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan [2] Research Center for Chinese Medicine &Acupuncture, China Medical University, Taichung, Taiwan.

1] National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan [2] Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.

出版信息

Sci Rep. 2015 Jul 28;5:12578. doi: 10.1038/srep12578.

The toll-like receptor 9 (TLR9) agonists CpG oligodeoxynucleotides (CpG ODNs) have been recognized as promising adjuvants for vaccines against infectious diseases and cancer. However, the role of TLR9 signaling in the regulation of antigen uptake and presentation is not well understood. Therefore, to investigate the effects of TLR9 signaling, this study used synthetic peptides (IDG) and lipopeptides (lipoIDG), which are internalized by dendritic cells (DCs) via endocytosis-dependent and endocytosis-independent pathways, respectively. Our data demonstrated that the internalization of lipoIDG and IDG by bone marrow-derived dendritic cells (BMDCs) was not enhanced in the presence of CpG ODNs; however, CpG ODNs prolonged the co-localization of IDG with CpG ODNs in early endosomes. Surprisingly, CpG ODNs enhanced CD8(+) T cell responses, and the anti-tumor effects of IDG immunization were stronger than those of lipoIDG immunization. LipoIDG admixed with CpG ODNs induced low levels of CD8(+) T cells and partially inhibit tumor growth. Our findings suggest that CpG ODNs increase the retention of antigens in early endosomes, which is important for eliciting anti-tumor immunity. These results will facilitate the application of CpG adjuvants in the design of different vaccines.

Toll样受体9（TLR9）激动剂CpG寡脱氧核苷酸（CpG ODNs）已被公认为是用于预防传染病和癌症疫苗的有前景的佐剂。然而，TLR9信号在调节抗原摄取和呈递中的作用尚未得到充分了解。因此，为了研究TLR9信号的作用，本研究使用了合成肽（IDG）和脂肽（lipoIDG），它们分别通过内吞作用依赖性和内吞作用非依赖性途径被树突状细胞（DCs）内化。我们的数据表明，在存在CpG ODNs的情况下，骨髓来源的树突状细胞（BMDCs）对lipoIDG和IDG的内化并未增强；然而，CpG ODNs延长了IDG与早期内体中CpG ODNs的共定位。令人惊讶的是，CpG ODNs增强了CD8(+) T细胞反应，并且IDG免疫的抗肿瘤作用比lipoIDG免疫更强。与CpG ODNs混合的lipoIDG诱导低水平的CD8(+) T细胞并部分抑制肿瘤生长。我们的研究结果表明，CpG ODNs增加了抗原在早期内体中的保留，这对于引发抗肿瘤免疫很重要。这些结果将有助于CpG佐剂在不同疫苗设计中的应用。