自噬增强外泌体介导的抗原递呈在抗淋巴瘤中的作用及机制研究

肿瘤外泌体TEX是DC负载抗原的天然转运载体，其携带的肿瘤相关特异性抗原，被DC摄取后（即TEX-DC疫苗）能有效的诱导CD8+T细胞活性而发挥特异抗肿瘤作用，然而单纯肿瘤来源的TEX产生的抗肿瘤免疫反应相对较弱。研究发现自噬不仅在DC的抗原递呈中起关键作用，且与内吞-外泌体途径在肿瘤抗原加工和递呈过程中存在相互调节作用，因此，靶向修饰自噬可能是提高TEX-DC疫苗的抗肿瘤活性而彻底清除肿瘤残留病灶的新策略。我们前期研究发现淋巴瘤来源的TEX不仅携带有淋巴瘤特异性蛋白，且被DC摄取后能有效的诱导CD8+T细胞活性而发挥有效抗淋巴瘤作用，在此基础上，本项目将进一步研究自噬增强TEX-DC在抗淋巴瘤中的作用及机制。

Tumor cell-derived exosome (TEX) harbors specific tumor-associated antigens, which can be efficiently taken up by DC (also named as TEX-DC vaccine ) and activates CD8+T cells, thereby eliciting specific anti-cancer immunity. However, the anti-tumor immune responses induced by TEXs are mild, and thus, many strategies have been adopted to develop modified TEXs to elicit a more efficient antitumor immune response. Recent studies suggest that autophagy not only plays a key role in antigen processing in DC, but has also been implicated in the endo-/ exosomal pathway in antigen processing for MHC presentation in anticancer T cell immune responses. Our previous study found that lymphoma-derived TEX carried lymphoma specific proteins, and could induce CD8+T cell activity after DC uptake, which played an anti-lymphoma effect. In this study, we will further investigate the effects and mechanisms of TEX-DC vaccine as a novel immunotherapy for lymphoma by targeting autophagy pathway.