Kill two birds with one stone: Reprogramming tumor microenvironment with growth differentiation factor 11.

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Hepatocellular carcinoma (HCC) aggressiveness is driven by immunosuppressive tumor-associated macrophages (TAMs).
• These M2-type macrophages promote tumor growth and metastasis by suppressing anti-tumor immunity.

Purpose of the Study:

• To investigate the potential of growth differentiation factor 11 (GDF11) in modulating TAMs and HCC progression.
• To determine if GDF11 can reverse the pro-tumoral phenotype of macrophages and inhibit HCC cell functions.

Main Methods:

• Assessing the effect of GDF11 on M2 macrophage markers and cellular metabolism.
• Measuring reactive oxygen species (ROS) production in macrophages treated with GDF11.
• Evaluating the impact of GDF11 on HCC cell proliferation and migration.

Main Results:

• GDF11 reduced M2 macrophage markers and rewired cellular metabolism.
• GDF11 boosted ROS production in macrophages, shifting them to an anti-tumor state.
• GDF11 treatment decreased HCC cell proliferation and migration.

Conclusions:

• GDF11 effectively re-educates pro-tumoral TAMs into an anti-tumoral phenotype.
• GDF11 exhibits a dual action by inhibiting HCC cell proliferation and metastasis.
• GDF11 represents a promising therapeutic strategy to enhance HCC immunotherapies.