Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction |
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Authors: | Jianye Xu Jian Zhang Zongpu Zhang Zijie Gao Yanhua Qi Wei Qiu Ziwen Pan Qindong Guo Boyan Li Shulin Zhao Xiaofan Guo Mingyu Qian Zihang Chen Shaobo Wang Xiao Gao Shouji Zhang Huizhi Wang Xing Guo Ping Zhang Rongrong Zhao Hao Xue Gang Li |
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Institution: | 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 |
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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.Subject terms: Cancer microenvironment, Autophagy |
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