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)

Guangping Zhang; Yanan Liao; Xiaoping Pan; Xiaoli Zhang

doi:10.21037/atm-21-6998

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)

Ann Transl Med. 2022 Feb;10(4):217. doi: 10.21037/atm-21-6998.

Authors

Guangping Zhang¹, Yanan Liao¹, Xiaoping Pan², Xiaoli Zhang³

Affiliations

¹ Department of Gynecology, Affiliated Huadu Hospital, Southern Medical University (People's Hospital of Huadu District), Guangzhou, China.
² Clinical Laboratory, Affiliated Huadu Hospital, Southern Medical University (People's Hospital of Huadu District), Guangzhou, China.
³ Department of Obstetrics, Affiliated Huadu Hospital, Southern Medical University (People's Hospital of Huadu District), Guangzhou, China.

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.

Keywords: Cervical cancer; HPV-16 E7 (HPV16E7); dendritic cells (DCs); exosomes; macrophages.