mRNA Nanoparticles Reprogrammed Tumour-Supporting Immune Cells in Mice

Solid tumours often contain immune cells that protect the cancer instead of attacking it. A team led by Adelaide University has now tested a way to change the behaviour of one such population from inside the tumour. Its lipid nanoparticles carried messenger RNA and an immune-stimulating compound directly toward tumour-associated macrophages, commonly shortened to TAMs.

The particles were coated with an antibody that recognises TREM2, a protein found at high levels on these macrophages. After entering the cells, the particles released mRNA encoding CXCL9 and the compound resiquimod. CXCL9 is a chemical signal that attracts cytotoxic CD8-positive T cells. Resiquimod helped push the macrophages away from their immune-suppressing state.

In the mouse experiments, the formulation cut the share of suppressive macrophages by more than 60% and increased tumour CXCL9 levels fourfold.

The researchers also measured more cancer-fighting T cells and stronger T-cell activity inside the tumours. Tumour growth declined moderately. The result matters because immune checkpoint drugs can struggle when T cells cannot enter a tumour or remain active once they arrive.

A useful negative result

The team also combined the nanoparticles with drugs that block PD-L1 and CTLA-4. That combination increased cancer-fighting T cells further and produced central memory T cells, a population associated with longer-lasting immune responses. But it did not slow tumour growth more than the nanoparticle treatment alone in this mouse model.

That distinction keeps the finding grounded. More immune activity is not automatically the same as better tumour control. Researchers will need to determine whether the formulation works across other tumour models, how long its effects last, and whether targeting TREM2 avoids harmful immune changes elsewhere in the body.

The approach is different from simply destroying macrophages. It tries to turn cells already present in the tumour into local signal producers. A recent NewTqnia report showed another way that tumours can recruit immune cells to support their growth, illustrating why the surrounding immune environment has become a major treatment target.

The peer-reviewed study appeared in Science Advances on September 11, 2026. The next tests will need to separate a promising immune mechanism from a therapy capable of producing durable tumour control.