Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity.

Santiago Zelenay, Annemarthe G van der Veen, Jan P Böttcher, Kathryn J Snelgrove, Neil Rogers, Sophie E Acton, Probir Chakravarty, Maria Romina Girotti, Richard Marais, Sergio A Quezada, Erik Sahai, Caetano Reis e Sousa

Research output: Contribution to journalArticlepeer-review


The mechanisms by which melanoma and other cancer cells evade anti-tumor immunity remain incompletely understood. Here, we show that the growth of tumors formed by mutant Braf(V600E) mouse melanoma cells in an immunocompetent host requires their production of prostaglandin E2, which suppresses immunity and fuels tumor-promoting inflammation. Genetic ablation of cyclooxygenases (COX) or prostaglandin E synthases in Braf(V600E) mouse melanoma cells, as well as in Nras(G12D) melanoma or in breast or colorectal cancer cells, renders them susceptible to immune control and provokes a shift in the tumor inflammatory profile toward classic anti-cancer immune pathways. This mouse COX-dependent inflammatory signature is remarkably conserved in human cutaneous melanoma biopsies, arguing for COX activity as a driver of immune suppression across species. Pre-clinical data demonstrate that inhibition of COX synergizes with anti-PD-1 blockade in inducing eradication of tumors, implying that COX inhibitors could be useful adjuvants for immune-based therapies in cancer patients.
Original languageEnglish
Pages (from-to)1257-1270
Issue number6
Publication statusPublished - 10 Sept 2015

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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