如何激活肿瘤免疫微环境是当前肿瘤免疫治疗亟需解决的焦点问题。课题组一直从事于寄生虫抗肺癌研究，发现减毒弓形虫(CPS)瘤内注射能诱导瘤体内效应性CD8+T细胞浸润增多，抑制HLA-A2小鼠A549瘤体生长；CPS入侵A549细胞释放的外泌体是激活瘤体DC细胞，进而活化效应性CD8+T细胞的关键因素；Label-free定量蛋白组学检测发现CPS入侵改变了A549细胞外泌体中蛋白成分，分析Uniprot数据库及文献发现上调外泌体Meosin蛋白（9.4倍）可能是CPS激活DC细胞的机制。鉴此，本项目拟在此基础上利用Meosin敲除证实CPS通过上调A549细胞外泌体Moesin蛋白激活DC，促使CD8+T细胞活化和浸润；初步探讨CPS上调外泌体Meosin蛋白的分子机制。这不但揭示了CPS激活A549实体瘤免疫微环境的新分子机制，也为寻找新的肿瘤免疫治疗分子靶点和方法提供了理论依据和数据支持

The studies of current tumor immunotherapy have been centered on how to activate tumor immune microenvironment or increase the infiltration of activated immune cells in tumor. Our group was engaged in the investigation of parasitic-immunity against lung cancer. In the former work of our laboratory, we found the attenuated toxoplasma gondii (CPS) could increase the infiltration of intratumoral effector CD8+T cells and inhibit the growth of subcutaneous tumor in HLA-A2 mice by intratumoral injection. The exosomes released from A549 cells invaded by CPS can induce the mature of DC cells，and then CD8+T cells were activated by the DC cells. The results of label-free quantitative proteomics showed that the protein composition of A549 cell exosomes was changed by CPS invading, Uniprot database and literature analysis showed that upregulation of exosome Meosin protein (9.4 times) may be the mechanism of CPS activating DC cells. In view of this, this project intends to use Meosin knockout A549 cells on this basis to confirm that CPS activates DC by upregulation of Meosin protein in A549 exosomes to promote CD8+T cell activation and infiltration. The molecular mechanism of Meosin protein upregulation by CPS was discussed. This not only revealed the new molecular mechanism of activation of A549 solid tumor immune microenvironment mediated by CPS, but also provided theoretical basis and data support for the search for new tumor immunotherapy molecular targets and methods.