CAFs-TAMs-tumor cells调控在HRHPV感染致癌中的作用机制研究及AI可追溯预测模型建立

宫颈癌中的肿瘤相关成纤维细胞（CAFs）对肿瘤相关巨噬细胞（TAMs）活化与极化的调控是肿瘤免疫微环境的主要内容。CAFs、TAMs、肿瘤细胞三者之间相互调控形成免疫抑制性微环境，逃避免疫监视，但‘CAFs-TAMs-tumor cells’调控机制尚不清楚。前期发现，CAFs促进成瘤与转移，CAFs促进TAMs M2极化；CAFs来源的外泌体（CAFs-Exo）促进细胞增殖；CAFs-Exo中的miR-146a表达水平上调。因此推测：CAFs通过外泌体-miR-146a诱导TAM M2极化促进宫颈癌进展。我们将使用类器官模型研究CAFs-Exo对TAMs M2极化的促进及其在宫颈癌进展中的作用；证明CAFs-Exo介导miR-146a从CAFs向TAMs迁移；证实miR-146a诱导TAMs M2极化并鉴定新的靶基因；运用人工智能技术建立预测模型。以期为宫颈癌诊、治新方法的建立奠定基础。

The regulation of tumor-associated fibroblasts (CAFs) on the activation and polarization of tumor-associated macrophages (TAMs) in cervical cancer is the main content of tumor immune microenvironment. CAFs, TAMs and tumor cells regulate each other to form an immunosuppressive microenvironment and evade immune surveillance, but the specific regulatory mechanism of 'CAFs-TAMs-tumor cells' remains unclear. Previous studies have revealed that CAFs promote tumor formation and metastasis, and CAFs promote TAMs M2 polarization. CAFs-derived exosomes (CAFs-exo) promote cell proliferation. MiR-146a expression in CAFs-exo was up-regulated. Therefore, it was speculated that CAFs induced TAM M2 polarization through exosome-miR-146a to promote the progression of cervical cancer. We intend to further investigate the promotion of CAFs-exo on TAMs M2 polarization and its role in the progression of cervical cancer with organoid model, and prove that CAFs-exo mediate the migration of miR-146a from CAFs to TAMs, miR-146a induces TAMs M2 polarization. Also, new target genes will be identified. We will build prediction model with artificial intelligence technology. In order to lay a foundation, for the establishment of new methods of cervical cancer diagnosis and treatment.