Promoting antibody-dependent cellular phagocytosis for effective macrophage-based cancer immunotherapy

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Macrophages are crucial for antibody-dependent cellular phagocytosis (ADCP) of cancer cells.
• ADCP efficacy is limited by early antibody administration and resistance during cancer progression.

Purpose of the Study:

• To investigate ADCP mechanisms and develop a combinatorial strategy to enhance its efficacy.
• To identify agents that potentiate ADCP by anticancer antibodies.

Main Methods:

• Investigated paclitaxel as an adjuvant for ADCP.
• Analyzed macrophage polarization and CSF1R expression in response to paclitaxel.
• Assessed the impact of paclitaxel-induced CSF1R down-regulation on ADCP.

Main Results:

• Paclitaxel universally potentiated ADCP across various cancer types and antibodies.
• Paclitaxel polarized macrophages towards enhanced phagocytic activity, not direct cytotoxicity.
• Paclitaxel-treated macrophages exhibited down-regulated CSF1R, which correlated with improved patient survival and enhanced ADCP.

Conclusions:

• Paclitaxel serves as a potent adjuvant to stimulate macrophage phagocytosis.
• Down-regulation of CSF1R on macrophages enhances ADCP of cancer cells.
• Combining conventional anticancer drugs with antibodies offers a promising strategy to improve cancer therapy.