Zhang Guangping, Liao Yanan, Pan Xiaoping, Zhang Xiaoli
Department of Gynecology, Affiliated Huadu Hospital, Southern Medical University (People's Hospital of Huadu District), Guangzhou, China.
Clinical Laboratory, Affiliated Huadu Hospital, Southern Medical University (People's Hospital of Huadu District), Guangzhou, China.
Ann Transl Med. 2022 Feb;10(4):217. doi: 10.21037/atm-21-6998.
Cervical cancer is mainly caused by persistent infection with human papillomavirus (HPV), especially HPV-16. Recently, HPV-16 E7-modified dendritic cells (DCs) have been reported to play a blocking role in the progression of cervical cancer. Conversely, the effect and mechanism of HPV-16 E7-pulsed DCs in cervical cancer are not entirely clear.
DCs from the peripheral blood of patients with cervical cancer were induced with lipopolysaccharide and identified through the detection of cluster of differentiation (CD)11c, major histocompatibility complex (MHC)-II, CD83, and CD40 levels, and exosomes from HPV-16 E7-pulsed and catalase 2 (CAT2)-silenced DCs were extracted and identified through transmission electron microscopy and the detection of markers. Additionally, the migration, inflammatory factors, and polarization of macrophages were confirmed using Transwell, enzyme-linked immunoassay, and Western blot of arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS). , we also built a mice xenograft model of HPV cervical cancer.
We first successfully induced and identified DCs from cervical cancer patients, and successfully extracted and confirmed the exosomes from the constructed HPV-16 E7-pulsed and CAT2-silenced DCs. Subsequently, we proved that exosomes from HPV-16 E7-pulsed DCs restrained migration and inflammation and induced M2 polarization in macrophages, while the effect of exosomes from CAT2-silenced DCs on macrophage migration, polarization, and inflammation was opposite to that of exosomes from HPV-16 E7-pulsed DCs, and the 2 affected each other. Additionally, we found that exosomes from CAT2-silenced DCs also prevented growth and M2 polarization in a mice xenograft model of HPV cervical cancer.
Exosomes from HPV-16 E7-pulsed DCs blocked cervical cancer progression by regulating macrophage function, and its mechanism was relevant to CAT2.
宫颈癌主要由人乳头瘤病毒（HPV）持续感染引起，尤其是HPV - 16。最近，有报道称HPV - 16 E7修饰的树突状细胞（DCs）在宫颈癌进展中起阻断作用。相反，HPV - 16 E7脉冲DCs在宫颈癌中的作用和机制尚不完全清楚。
用脂多糖诱导宫颈癌患者外周血中的DCs，并通过检测分化簇（CD）11c、主要组织相容性复合体（MHC） - II、CD83和CD40水平进行鉴定，提取HPV - 16 E7脉冲和过氧化氢酶2（CAT2）沉默DCs的外泌体，并通过透射电子显微镜和标志物检测进行鉴定。此外，使用Transwell、酶联免疫吸附测定以及精氨酸酶 - 1（Arg - 1）和诱导型一氧化氮合酶（iNOS）的蛋白质印迹法来确认巨噬细胞的迁移、炎症因子和极化情况。我们还建立了HPV宫颈癌小鼠异种移植模型。
我们首先成功诱导并鉴定了来自宫颈癌患者的DCs，并成功提取并确认了构建的HPV - 16 E7脉冲和CAT2沉默DCs的外泌体。随后，我们证明HPV - 16 E7脉冲DCs的外泌体抑制了巨噬细胞的迁移和炎症，并诱导其向M2极化，而CAT2沉默DCs的外泌体对巨噬细胞迁移、极化和炎症的影响与HPV - 16 E7脉冲DCs的外泌体相反，且二者相互影响。此外，我们发现CAT2沉默DCs的外泌体在HPV宫颈癌小鼠异种移植模型中也能阻止肿瘤生长和M2极化。
HPV - 16 E7脉冲DCs的外泌体通过调节巨噬细胞功能阻断宫颈癌进展，其机制与CAT2相关。
