Potentiation of cancer immunotherapy using spatiotemporal regulation of heat shock protein-TLR ligand complex

我们已经证明，Hsp90可以通过时空调节作为相关抗原肽交叉表达的有效诱导剂。我们研究了hsp90抗原肽复合物和TLR配体是否通过交叉表达增强了细胞毒性T细胞（CTL）反应的诱导。有趣的是，浆细胞样树突状细胞（pDCs）在CpG-A的作用下不仅分泌IFN-a，还分泌Hsp72。我们发现分泌的Hsp72与hsp90肽复合物形成复合物，导致有效的交叉表达和对相关肽的CTL诱导。这些数据表明CpG-A是基于hsp90的癌症疫苗的良好候选免疫佐剂。

We have demonstrated that Hsp90 can act as an efficient inducer for crosspresentation of associated antigenic peptide via spatiotemporal regulation. We examined whether vaccination with Hsp90-antigen peptide complex and TLR ligand augmented the induction of cytotoxic T cell (CTL) response via crosspresentation. Interestingly, plasmacytoid dendritic cells (pDCs) secreted not only IFN-a but also Hsp72 in response to CpG-A administration. We found that the secreted Hsp72 formed complex with Hsp90-peptide complex, leading to the efficient crosspresentation and CTL induction against associated peptide. These data suggest that CpG-A is a good candidate as an immunoadjuvant for Hsp90-based cancer vaccine.