Exosomes from HPV-16 E7-pulsed dendritic cells prevent the migration, M1 polarization, and inflammation of macrophages in cervical cancer by regulating catalase 2 (CAT2).

ABSTRACT:

Background

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.

Methods

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). In vivo, we also built a mice xenograft model of HPV cervical cancer.

Results

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.

Conclusions

Exosomes from HPV-16 E7-pulsed DCs blocked cervical cancer progression by regulating macrophage function, and its mechanism was relevant to CAT2.

SUBMITTER: Zhang G 

PROVIDER: S-EPMC8908111 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature