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Are TEMs Canceled? Questioning the Functional Relevance of Tie2-Expressing Macrophages
Yuqing Zhang1,2, Rolf A Brekken1,2,3
1Cancer Biology Graduate Program, UT Southwestern Medical Center, Dallas, Texas.
Abstract:
Inflammatory cells are a vital component of the tumor stroma and, of these, tumor-associated macrophages (TAM) are the major cell type. TAMs are recruited early in tumorigenesis and generally promote metastasis, stimulate tumor angiogenesis, and drive immunosuppression. TAMs have been shown to express the endothelial cell markers that enable chemotaxis and proangiogenic capacity. In this issue of Cancer Research, Jakab and colleagues challenge the functional significance of Tie2-expressing monocytes/macrophages (TEM) in the context of tumor growth and progression. By employing myeloid-specific deletion of the angiopoietin receptor Tie2 and comprehensive analysis of myeloid cell single-cell RNA sequencing datasets, they provide compelling data that Tie2-positive macrophages do not contribute to tumor angiogenesis or relapse after chemotherapy, two major biologic processes previously attributed to tumor-associated TEMs. The study highlights that the concept of macrophage-expressed Tie2 as a therapeutic target or prognostic indicator needs reconsideration. See related article by Jakab et al., p. 1353.
Insights
This study reveals that Tie2-positive macrophages do not drive tumor angiogenesis or chemotherapy relapse. These findings challenge the role of Tie2-expressing monocytes/macrophages (TEM) as therapeutic targets in cancer progression.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tumor-associated macrophages (TAMs) are key players in tumor stroma, promoting metastasis, angiogenesis, and immunosuppression.
- TAMs express endothelial markers, suggesting a role in chemotaxis and proangiogenic functions.
- Tie2-expressing monocytes/macrophages (TEM) have been implicated in tumor growth and progression.
Purpose of the Study:
- To investigate the functional significance of Tie2-expressing monocytes/macrophages (TEM) in tumor growth and progression.
- To determine the contribution of Tie2-positive macrophages to tumor angiogenesis and chemotherapy relapse.
Main Methods:
- Myeloid-specific deletion of the angiopoietin receptor Tie2 in a tumor model.
- Comprehensive analysis of myeloid cell single-cell RNA sequencing datasets.
- Functional assays to assess tumor angiogenesis and relapse after chemotherapy.
Main Results:
- Tie2-positive macrophages do not significantly contribute to tumor angiogenesis.
- Absence of Tie2-positive macrophages did not affect tumor relapse after chemotherapy.
- Data challenges the established role of TEM in promoting these critical tumor processes.
Conclusions:
- The concept of macrophage-expressed Tie2 as a direct therapeutic target or prognostic indicator in cancer requires re-evaluation.
- Further research is needed to elucidate the precise roles of different macrophage populations in tumorigenesis.
- These findings may necessitate a shift in therapeutic strategies targeting TAMs.
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