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...
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BMC
2025-01-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13046-025-03287-w |
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| author | Hanrui Guo Meiling Wang Caiya Ni Chun Yang Chunxue Fu Xiaoman Zhang Xueling Chen Xiangwei Wu Jun Hou Lianghai Wang |
| author_facet | Hanrui Guo Meiling Wang Caiya Ni Chun Yang Chunxue Fu Xiaoman Zhang Xueling Chen Xiangwei Wu Jun Hou Lianghai Wang |
| author_sort | Hanrui Guo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2bf6f9c125374b6193451eb51d731fb3 |
| institution | Kabale University |
| issn | 1756-9966 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj-art-2bf6f9c125374b6193451eb51d731fb32025-01-26T12:57:56ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662025-01-0144111410.1186/s13046-025-03287-wTREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinomaHanrui Guo0Meiling Wang1Caiya Ni2Chun Yang3Chunxue Fu4Xiaoman Zhang5Xueling Chen6Xiangwei Wu7Jun Hou8Lianghai Wang9Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineAbstract 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.https://doi.org/10.1186/s13046-025-03287-wTREM2HCCCD8GlycolysisPKM2 |
| spellingShingle | Hanrui Guo Meiling Wang Caiya Ni Chun Yang Chunxue Fu Xiaoman Zhang Xueling Chen Xiangwei Wu Jun Hou Lianghai Wang TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma Journal of Experimental & Clinical Cancer Research TREM2 HCC CD8 Glycolysis PKM2 |
| title | TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma |
| title_full | TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma |
| title_fullStr | TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma |
| title_full_unstemmed | TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma |
| title_short | TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma |
| title_sort | trem2 promotes the formation of a tumor supportive microenvironment in hepatocellular carcinoma |
| topic | TREM2 HCC CD8 Glycolysis PKM2 |
| url | https://doi.org/10.1186/s13046-025-03287-w |
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