IL-2 Modulates TAMs Derived Exosomal MiRNAs to Ameliorate Hepatocellular Carcinoma Development and Progression

Hao Chen; Chao Tang; Chun Tan; Fei Wu; Zhenhan Li; Wenyan Ji; Linming Lu; Chongjun Xu; Zhengchao Shen; Yanqiang Huang

doi:10.1155/2022/3445350

IL-2 Modulates TAMs Derived Exosomal MiRNAs to Ameliorate Hepatocellular Carcinoma Development and Progression

J Oncol. 2022 Feb 21:2022:3445350. doi: 10.1155/2022/3445350. eCollection 2022.

Authors

Hao Chen^{1

2

3}, Chao Tang⁴, Chun Tan⁵, Fei Wu⁶, Zhenhan Li⁶, Wenyan Ji⁷, Linming Lu², Chongjun Xu⁶, Zhengchao Shen⁸, Yanqiang Huang¹

Affiliations

¹ Research Center for the Prevention and Treatment of Drug Resistant Microbial Infecting, Youjiang Medical University for Nationalities, Baise 533000, China.
² Department of Pathology, Wannan Medical College, Wuhu 241002, China.
³ Postdoctoral Research Station of Clinical Medicine, Jinan University, Guangzhou 510632, China.
⁴ School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
⁵ Graduate School, Youjiang Medical University for Nationalities, Baise 533000, China.
⁶ School of Clinical Medicine, Wannan Medical College, Wuhu 241002, China.
⁷ Department of Ultrasound, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu 241002, China.
⁸ Department of Hepatobiliary Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu 241001, China.

Abstract

Background. Interleukin-2 (IL-2) is proved to play an irreplaceable role in antitumor regulation in numerous experimental and clinical trials. Tumor-associated macrophages (TAMs) are able to release exosomes to promote the development and progression of hepatocellular carcinoma (HCC) as essential component of microenvironment. In this study, our intention is to explore the effects of the exosomes from TAMs with IL-2 treatment on HCC development. TAMs were collected and cultured from HCC tissues. The exosomes from the TAMs treated with IL-2 (Exo^IL2-TAM) or not (Exo^TAM) were identified and used to treat HCC cells in vivo and in vitro. The proliferation, apoptosis, and metastasis of HCC cells were measured. The changes of miRNAs in exosomes were explored to clarify the possible mechanisms. Both decrease of cell proliferation and metastasis and increase of apoptosis were observed with Exo^IL2-TAM treatment compared with Exo^TAM in vivo and in vitro. miR-375 was obviously augmented in Exo^IL2-TAM and HCC cells treated with Exo^IL2-TAM. Taken together, IL-2 may modulate exosomal miRNAs from TAMs to ameliorate hepatocellular carcinoma development. This study provides a new perspective to explain the mechanism by which IL-2 inhibits hepatocellular carcinoma and implies the potential clinical value of exosomal miRNAs released by TAMs.