Exosomes Derived From Dendritic Cells Infected With Toxoplasma gondii Show Antitumoral Activity in a Mouse Model of Colorectal Cancer

被引：22

作者：

Lu, Jinmiao ^{[1
,2
]}

Wei, Nana ^{[3
]}

Zhu, Shilan ^{[1
,2
]}

Chen, Xiaoyu ^{[1
,2
]}

Gong, Haiyan ^{[2
]}

Mi, Rongsheng ^{[2
]}

Huang, Yan ^{[2
]}

Chen, Zhaoguo ^{[2
]}

Li, Guoqing ^{[1
]}

机构：

[1] South ChinaAgricultural Univ, Coll Vet Med, Guangdong Prov Key Lab Zoonosis Prevent & Control, Guangzhou, Peoples R China

[2] Chinese Acad Agr Sci, Shanghai Vet Res Inst, Key Lab Anim Parasitol Minist Agr, Lab Qual, Shanghai, Peoples R China

[3] East China Normal Univ, Key Lab AdolescentHealth Assessment, Exercise Intervent Minist Educ, Shanghai, Peoples R China

来源：

FRONTIERS IN ONCOLOGY | 2022年 / 12卷

基金：

中国国家自然科学基金;

关键词：

Toxoplasma gondii; exosomes; myeloid derived suppressor cells (MDSCs); dendritic cells (DCs); colorectal cancer (CRC); immunosuppression; SUPPRESSOR-CELLS; DIFFERENTIATION; ACCUMULATION; INHIBITION; MECHANISM; TUMORS;

D O I：

10.3389/fonc.2022.899737

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Pathogen-based cancer therapies have been widely studied. Parasites, such as Toxoplasma gondii have elicited great interest in cancer therapy. Considering safety in clinical applications, we tried to develop an exosome-based immunomodulator instead of a live parasite for tumor treatment. The exosomes, called DC-Me49-exo were isolated from culture supernatants of dendritic cells (DCs) infected with the Me49 strain of T. gondii and identified. We assessed the antitumoral effect of these exosomes in a mouse model of colorectal cancer (CRC). Results showed that the tumor growth was significantly inhibited after treatment with DC-Me49-exo. Proportion of polymorphonuclear granulocytic bone marrow-derived suppressor cells (G-MDSCs, CD11b(+)Ly6G(+)) and monocytic myeloid-derived suppressor cells (M-MDSCs, CD11b(+)Ly6C(+)) were decreased in the DC-Me49-exo group compared with the control groups in vitro and in vivo. The proportion of DCs (CD45(+)CD11c(+)) increased significantly in the DC-Me49-exo group. Levels of interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly decreased after treatment with DC-Me49-exo. Furthermore, we found that DC-Me49-exo regulated the lever of MDSC mainly by inhibiting the signal transducer and activator of transcription (STAT3) signaling pathway. These results indicated that exosomes derived from DCs infected with T. gondii could be used as part of a novel cancer therapeutic strategy by reducing the proportion of MDSCs.

引用

页数：10

共 30 条

[11]

Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer [J].