TREM2 Promotes the Formation of a Tumor-supportive Microenvironment in Hepatocellular Carcinoma

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Date 2025 Jan 22

PMID 39838454

Authors

Hanrui Guo

Meiling Wang

Caiya Ni

Chun Yang

Chunxue Fu

Xiaoman Zhang

Xueling Chen

Xiangwei Wu

Jun Hou

Lianghai Wang

Affiliations

Soon will be listed here.

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.

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