The COX-2/PGE2 pathway is commonly upregulated in multiple tumours. Here, the authors show that this inflammatory axis drives malignant growth by enabling immune escape and that cyclooxygenase inhibitors synergise with immunotherapy to promote tumour eradication.

Natural killer cells recruit dendritic cells to the tumour microenvironment, and disruption of this process results in cancer immune evasion.

The authors demonstrate that cancer cell-derived PGE2, acting on EP2 and EP4 on NK cells, restrains T cell-dependent tumour control and devise a COX-2-associated inflammatory signature that predicts patient survival and response to immunotherapy.

Through in-depth cellular and molecular profiling of mice and human tumours, the authors identify the mechanisms by which anti-inflammatory drugs targeting the COX-2/PGE2/EP2-4 axis rapidly alter the tumour immune landscape to enhance the response to immune checkpoint inhibition.

Evangelos Giampazolias received £1.8m in EU funding to pursue cutting-edge research in cancer immunity in Manchester.