Статья

Exosomes Released from Tumor-Associated Macrophages Transfer miRNAs That Induce a Treg/Th17 Cell Imbalance in Epithelial Ovarian Cancer

Jieru Zhou1Department of Obstetrics and Gynaecology, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaXiaoduan Li2Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaXiaoli Wu1Department of Obstetrics and Gynaecology, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaTing Zhang3Center for Reproductive Medicine, Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, ChinaQinyi Zhu2Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaXinjing Wang1Department of Obstetrics and Gynaecology, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaHusheng Wang1Department of Obstetrics and Gynaecology, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaKai Wang2Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaYingying Lin4Department of Neurosurgery, RenJi Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, ChinaXipeng Wang1Department of Obstetrics and Gynaecology, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

2018en

ABI

Аннотация

Abstract The immune microenvironment is crucial for epithelial ovarian cancer (EOC) progression and consists of tumor-associated macrophages (TAM) and T lymphocytes, such as regulatory T cells (Treg) and T helper 17 (Th17) cells. In this study, the Treg/Th17 ratio was significantly higher in EOC in situ and in metastatic peritoneal tissues than in benign ovarian tumors and benign peritoneum. The Treg/Th17 ratio was associated with histologic grade and was an independent prognostic factor for overall survival of EOC patients. On the basis of microarray analysis of exosomes derived from TAMs, we identified miRNAs enriched in the exosomes, including miR-29a-3p and miR-21-5p. When the two miRNA mimics were transfected into CD4+ T cells, they directly suppressed STAT3 and regulated Treg/Th17 cells, inducing an imbalance, and they had a synergistic effect on STAT3 inhibition. Taken together, these results indicate that exosomes mediate the interaction between TAMs and T cells, generating an immune-suppressive microenvironment that facilitates EOC progression and metastasis. These findings suggest that targeting these exosomes or their associated miRNAs might pave the way for the development of novel treatments for EOC.

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Идентификаторы

DOI: 10.1158/2326-6066.cir-17-0479

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar