2. Academic Validation
  3. TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma

TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma

  • J Exp Clin Cancer Res. 2025 Jan 21;44(1):20. doi: 10.1186/s13046-025-03287-w.
Hanrui Guo # 1 2 3,  Meiling Wang # 1 2 4,  Caiya Ni # 1 2,  Chun Yang # 1 2 5,  Chunxue Fu 1 2,  Xiaoman Zhang 1 2,  Xueling Chen 1 2,  Xiangwei Wu 1 2,  Jun Hou 6 7,  Lianghai Wang 8 9
Affiliations

Affiliations

  • 1 Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
  • 2 NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
  • 3 Department of Clinical Laboratory, Jinan Maternity and Child Care Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, China.
  • 4 Department of Pathology, Jinan Maternity and Child Care Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, China.
  • 5 Department of Pathology, Affiliated Tianfu Hospital of Southwest Medical University (Meishan Tianfu New Area People's Hospital), Meishan, Sichuan, China.
  • 6 Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China. houjun229@163.com.
  • 7 NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China. houjun229@163.com.
  • 8 Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China. lh_wang@shzu.edu.cn.
  • 9 NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China. lh_wang@shzu.edu.cn.
  • # Contributed equally.
PMID: 39838454 DOI: 10.1186/s13046-025-03287-w
Abstract

Background: Triggering receptor expressed on myeloid cells 2 (TREM2), a surface receptor predominantly expressed on myeloid cells, is a major hub gene in pathology-induced immune signaling. However, its function in hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the role of TREM2 in the tumor microenvironment in the context of HCC progression.

Methods: HCC was experimentally induced in wild-type (WT) and Trem2-deficient (Trem2-/-) mice, and clinical sample analysis and in vitro studies on macrophages were conducted. HCC cells were treated with conditioned medium from WT or Trem2-/- macrophages, and their malignant phenotypes and underlying mechanisms were analyzed.

Results: TREM2 deficiency reduced liver tumor burden in orthotopic and subcutaneous HCC models by altering CD8+ T cell infiltration. Trem2-deficient macrophages presented increased chemokine secretion. TGF-β1 was found to be positively correlated with TREM2 expression in HCC, and TGF-β blockade reversed TREM2 induction. On the Other hand, TREM2+ macrophages were found to be associated with glycolysis and PKM2 expression in HCC cells; this association may be related to the secretion of IL-1β, which enhances the malignant phenotypes of HCC cells.

Conclusions: These results reveal that TREM2+ macrophages play a driving role in HCC progression by suppressing CD8+ T cell infiltration and promoting tumor cell glycolysis, providing a new therapeutic target for HCC.

Keywords

CD8; Glycolysis; HCC; PKM2; TREM2.

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