Pleural cavity macrophages promote lung tumor establishment through tissue invasion

Circulating monocytes are recruited to inflamed tumor tissues, where they differentiate into mature macrophages during tumor growth and metastasis. Cavity macrophages establish a physiological checkpoint that constrains anti-tumor activity at peritoneal and pleural sites of cancer. To monitor these endogenous cavity macrophages in melanoma lung metastasis, we employed dual recombinases-mediated in vivo genetic lineage tracing techniques. Our findings revealed significant infiltration of cavity macrophages into lung tumor metastases. Furthermore, we developed a genetic strategy to specifically and efficiently eradicate these macrophages. Notably, targeting cavity macrophages through specific Gata6 deficiency or their ablation markedly suppressed lung tumor growth. These findings underscore the pivotal role of cavity macrophages in tumor growth and metastasis dynamics, suggesting that targeting these cells may represent a promising therapeutic strategy for managing tumor progression.