Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Vascular endothelial growth factor (VEGF) is crucial for blood vessel formation in both normal and cancerous tissues.
• Monoclonal antibodies (mAbs) targeting VEGF inhibit tumor growth, but resistance can develop.
• Understanding mechanisms of resistance is vital for improving anti-angiogenic therapies.

Purpose of the Study:

• To investigate the cellular and molecular mechanisms underlying tumor refractoriness to anti-VEGF therapy.
• To identify key cell types and pathways involved in mediating resistance to anti-angiogenic treatment.

Main Methods:

• Utilized murine cancer models and human patient data.
• Analyzed tumor infiltration by CD11b+Gr1+ myeloid cells.
• Performed gene expression analysis on myeloid cells from refractory tumors.
• Tested combination therapy with anti-VEGF and myeloid cell-targeting mAbs.

Main Results:

• Inherent refractoriness to anti-VEGF therapy correlates with CD11b+Gr1+ myeloid cell infiltration.
• Recruitment of these myeloid cells alone can induce refractoriness.
• Combining anti-VEGF treatment with myeloid cell-targeting mAbs significantly inhibits refractory tumor growth.
• Gene expression profiling revealed upregulated myeloid cell mobilization and recruitment genes in refractory tumor-associated myeloid cells.

Conclusions:

• Tumor refractoriness to anti-VEGF therapy is mediated by the tumor's capacity to prime and recruit CD11b+Gr1+ myeloid cells.
• Targeting myeloid cell recruitment presents a promising strategy to overcome resistance to anti-angiogenic treatments.
• Combination therapy approaches are effective in managing anti-VEGF resistant tumors.