2. Academic Validation
  3. Hypoxia-induced TREM1 promotes mesenchymal-like states of glioma stem cells via alternatively activating tumor-associated macrophages

Hypoxia-induced TREM1 promotes mesenchymal-like states of glioma stem cells via alternatively activating tumor-associated macrophages

  • Cancer Lett. 2024 Mar 11:216801. doi: 10.1016/j.canlet.2024.216801.
Minhai Dong 1,  Xiaolin Zhang 2,  Peng Peng 3,  Zirong Chen 1,  Yang Zhang 4,  Lijun Wan 1,  Wang Xiang 1,  Guohao Liu 1,  Yang Guo 1,  Qungen Xiao 1,  Baofeng Wang 1,  Dongsheng Guo 1,  Min Zhu 5,  Xingjiang Yu 6,  Feng Wan 7
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 2 Department of Neurosurgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
  • 3 Department of Neurosurgery, Xiangyang Central Hospital, Affiliated Hospital to Hubei University of Arts and Science, Xiangyang, 4413000, China.
  • 4 Department of Histology and Embryology, College of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 5 Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: mzhu@tjh.tjmu.edu.cn.
  • 6 Department of Histology and Embryology, College of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: yuxingjiang@hust.edu.cn.
  • 7 Department of Neurosurgery, Xiangyang Central Hospital, Affiliated Hospital to Hubei University of Arts and Science, Xiangyang, 4413000, China. Electronic address: wanfeng@gdph.org.cn.
PMID: 38479552 DOI: 10.1016/j.canlet.2024.216801
Abstract

The mesenchymal subtype of glioblastoma (GBM) cells characterized by aggressive invasion and therapeutic resistance is thought to be dependent on cell-intrinsic alteration and extrinsic cellular crosstalk. Tumor-associated macrophages (TAMs) are pivotal in tumor progression, chemo-resistance, angiogenesis, and stemness maintenance. However, the impact of TAMs on the shifts in glioma stem cells (GSCs) states remains largely uncovered. Herein, we showed that the triggering receptor expressed on myeloid cells-1 (TREM1) preferentially expressed by M2-like TAMs and induced GSCs into mesenchymal-like states by modulating the secretion of TGFβ2, which activated the TGFβR/SMAD2/3 signaling in GSCs. Furthermore, we demonstrated that TREM1 was transcriptionally regulated by HIF1a under the hypoxic environment and thus promoted an immunosuppressive type of TAMs via activating the TLR2/Akt/mTOR/c-Myc axis. Collectively, this study reveals that cellular communication between TAMs and GSCs through the TREM1-mediated TGFβ2/TGFβR axis is involved in the mesenchymal-like transitions of GSCs. Our study provides valuable insights into the regulatory mechanisms between the tumor immune microenvironment and the malignant characteristics of GBM, which can lead to potential novel strategies targeting TAMs for tumor control.

Keywords

Glioma stem cells; Hypoxia; Mesenchymal-like states; TREM1; Tumor-associated macrophages.

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