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.

Cancer Research
|April 4, 2022
PubMed

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.