TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma
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 eva...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-025-03287-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 1756-9966 |