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Published on: October 14, 2015

Angiotensin-converting enzyme and the tumor microenvironment: mechanisms beyond angiogenesis

Derick Okwan-Duodu1, Jerome Landry, Xiao Z Shen

  • 1Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
|June 7, 2013
PubMed

Insights

The renin-angiotensin system (RAS) enzyme, angiotensin-converting enzyme (ACE), influences cancer by affecting the tumor microenvironment. ACE inhibitors may offer benefits in certain cancers by modulating immune cells and peptides.

Area of Science:

  • Oncology
  • Immunology
  • Cardiovascular Research

Background:

  • The renin-angiotensin system (RAS) regulates blood pressure and is implicated in cell proliferation and fibrosis.
  • Angiotensin-converting enzyme (ACE) is a key enzyme in the RAS, cleaving multiple substrates, including bradykinin and substance P.
  • ACE's role in cancer pathophysiology is increasingly recognized, particularly its influence on angiogenesis via the angiotensin II type 1 receptor (AT1R).

Purpose of the Study:

  • To review the role of ACE in modulating the immune compartment of the tumor microenvironment.
  • To discuss the impact of ACE and its peptide substrates on immunosuppressive cells like myeloid-derived suppressor cells, tumor-associated macrophages, and T regulatory cells.
  • To explore how peptides accumulating during ACE inhibitor use may affect anti-angiogenic therapies and cancer outcomes.

Main Methods:

  • Literature review of existing studies on ACE, the RAS, and cancer.
  • Analysis of the immunological components within the tumor microenvironment.
  • Discussion of the pharmacological effects of ACE inhibitors and related peptides.

Main Results:

  • ACE significantly influences the tumor microenvironment, particularly its immune components.
  • ACE modulates immunosuppressive cells, including myeloid-derived suppressor cells, alternatively activated tumor-associated macrophages, and T regulatory cells.
  • Accumulation of peptides like bradykinin and substance P due to ACE inhibition may counteract anti-angiogenic effects.

Conclusions:

  • ACE plays a multifaceted role in cancer beyond angiogenesis, impacting the tumor immune microenvironment.
  • Emerging mechanisms involving ACE and its substrates may explain conflicting results regarding ACE inhibitors in cancer.
  • Further research is warranted to investigate the potential therapeutic benefits of ACE inhibitors in specific cancer types.
Keywords:
T regulatory cellsangiogenesisangiotensin-converting enzymecancermacrophage polarizationmyeloid-derived suppressor cellstumor immunology

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