Anti-CD73 therapy impairs tumor angiogenesis

Area of Science:

• Immunology
• Cancer Biology
• Biochemistry

Background:

• CD73, an ecto-nucleotidase, is overexpressed in tumors and generates extracellular adenosine, an immunosuppressor.
• Extracellular adenosine influences hypoxia responses and adaptive immunity.
• The role of CD73 in tumor angiogenesis and the impact of anti-CD73 therapy on this process were previously unknown.

Purpose of the Study:

• To investigate the role of CD73 in tumor angiogenesis.
• To determine the effect of anti-CD73 therapy on tumor angiogenesis.

Main Methods:

• Utilized a mouse model of breast cancer.
• Assessed CD73 expression on tumor and host cells.
• Measured vascular endothelial growth factor (VEGF) levels.
• Evaluated endothelial cell function (tube formation, migration).
• Administered anti-CD73 monoclonal antibody therapy.

Main Results:

• CD73 expression on tumor and host cells contributes to tumor angiogenesis.
• Tumor-derived CD73 enhances VEGF production; host-derived CD73 is crucial for in vivo angiogenic responses.
• Endothelial cells require CD73 for tube formation and migration.
• Pro-angiogenic effects of CD73 involve both enzymatic and non-enzymatic functions.
• Anti-CD73 antibody treatment decreased tumor VEGF levels and suppressed angiogenesis in vivo.

Conclusions:

• CD73 plays a significant role in promoting tumor angiogenesis through both tumor and host cells.
• Targeted blockade of CD73 effectively inhibits tumor angiogenesis.
• Anti-CD73 therapy holds potential for clinical development in cancer treatment by targeting angiogenesis.