Gata6⁺ resident peritoneal macrophages promote the growth of liver metastasis

Area of Science:

• Immunology
• Oncology
• Cell Biology

Background:

• Resident macrophages are implicated in tumor progression.
• Large peritoneal macrophages (GLPMs) reside near visceral organs but their role in cancer is unknown.
• GLPMs can invade injured organs sensing danger signals.

Purpose of the Study:

• To investigate the role of GLPMs in liver metastasis.
• To understand the mechanisms by which GLPMs influence tumor growth and immune response.

Main Methods:

• Depletion of GLPMs using pharmacological and genetic tools.
• Analysis of GLPMs' interaction with tumor cells and immune cells.
• Administration of anti-PD-L1 therapy via intraperitoneal and intravenous routes.
• Assessment of tumor growth and recurrence after thermal ablation.

Main Results:

• GLPMs infiltrate liver metastases by sensing ATP.
• Depletion of GLPMs significantly reduces metastasis growth.
• Tumor cell apoptotic bodies upregulate PD-L1 on GLPMs, inhibiting CD8+ T cell function.
• Intraperitoneal anti-PD-L1 therapy reduces tumor growth, while intravenous administration is ineffective.
• Thermal ablation of metastases increases GLPM recruitment, leading to tumor regrowth.

Conclusions:

• GLPMs are critical drivers of liver metastatic growth and recurrence.
• Targeting GLPMs, particularly via PD-L1 blockade locally, offers a potential therapeutic strategy.