Preclinical studies indicate that cavity-resident macrophages in the peritoneal and pleural spaces contribute to immunosuppression and cancer progression.

While these macrophages typically accumulate on organ surfaces rather than deeply infiltrating into tissues, their behaviour and function in tumours remains unclear.

Using dual recombinase-mediated genetic lineage tracing in a B16F10 melanoma lung metastasis model, this study demonstrated that pleural cavity macrophages (GATA6⁺CD45⁺) infiltrate lung tumours and contribute to a significant proportion of tumour-associated macrophage.

Genetic ablation or sequestration of these macrophages markedly suppressed tumour growth, underscoring their pro-tumorigenic function.

To investigate their recruitment, Gata6-iCreER mice were crossed with Cd45-Dre and R26-tdT mice, enabling specific lineage tracing of cavity macrophages.

Flow cytometry and immunofluorescence confirmed their infiltration into lung tumours, where they constituted for ~50% of tumour-associated macrophages.

Similar observations were made in Hepa1-6 and LLC metastasis models, suggesting a broad role across tumour types.

To assess functional relevance, a Gata6-RSR-tdT-DTR mouse model was developed for diphtheria toxin (DT)-mediated macrophage depletion.

DT treatment significantly reduced tumour burden and extended survival, confirming their pro-tumour effects.

Gata6 knockout in cavity macrophages significantly suppressed metastasis.

However, cell depletion after tumour establishment showed limited efficacy, indicating their primary role in early tumour growth.

Mechanistically, macrophage depletion increased cytotoxic CD8⁺ T cells in tumours and pleural cavities, suggesting that cavity macrophages suppress anti-tumour immunity.

These findings establish cavity macrophages as key drivers of tumour progression and propose their targeting as a potential therapeutic strategy.

Further research is needed to elucidate the molecular mechanisms driving their migration and immunosuppressive functions.

Source: Higher Education Press