2. Academic Validation
  3. Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction

Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction

  • Cell Death Dis. 2021 Apr 7;12(4):373. doi: 10.1038/s41419-021-03664-1.
Jianye Xu  # 1 2,  Jian Zhang  # 1 2 3,  Zongpu Zhang 1 2,  Zijie Gao 1 2,  Yanhua Qi 1 2,  Wei Qiu 1 2,  Ziwen Pan 1 2,  Qindong Guo 1 2,  Boyan Li 1 2,  Shulin Zhao 1 2,  Xiaofan Guo 1 2,  Mingyu Qian 1 2,  Zihang Chen 1 2,  Shaobo Wang 1 2,  Xiao Gao 1 2,  Shouji Zhang 1 2,  Huizhi Wang 1 2,  Xing Guo 1 2,  Ping Zhang 1 2,  Rongrong Zhao 1 2,  Hao Xue 4 5,  Gang Li 6 7
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, Shandong, China.
  • 2 Shandong Key Laboratory of Brain Function Remodeling, Jinan, 250012, Shandong, China.
  • 3 Department of Neurosurgery, Dezhou People's Hospital, Dezhou, 253000, Shandong, China.
  • 4 Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, Shandong, China. [email protected].
  • 5 Shandong Key Laboratory of Brain Function Remodeling, Jinan, 250012, Shandong, China. [email protected].
  • 6 Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, Shandong, China. [email protected].
  • 7 Shandong Key Laboratory of Brain Function Remodeling, Jinan, 250012, Shandong, China. [email protected].
  • # Contributed equally.
PMID: 33828078 DOI: 10.1038/s41419-021-03664-1
Abstract

Exosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the generation of the immunosuppressive microenvironment are still unclear. Here, we investigated the effects of GDEs on Autophagy, the polarization of tumor-associated macrophages (TAMs), and glioma progression. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly facilitated Autophagy and M2-like macrophage polarization, which subsequently promoted glioma proliferation and migration in vitro and in vivo. Western blot and qRT-PCR analyses indicated that interleukin 6 (IL-6) and miR-155-3p were highly expressed in H-GDEs. Further experiments showed that IL-6 and miR-155-3p induced M2-like macrophage polarization via the IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3 positive feedback loop, which promotes glioma progression. Our study clarifies a mechanism by which hypoxia and glioma influence Autophagy and M2-like macrophage polarization via exosomes, which could advance the formation of the immunosuppressive microenvironment. Our findings suggest that IL-6 and miR-155-3p may be novel biomarkers for diagnosing glioma and that treatments targeting Autophagy and the STAT3 pathway may contribute to antitumor immunotherapy.

Figures
Products