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The mechanisms by which melanoma and other cancer cells evade anti-tumor immunity remain incompletely understood. This study shows that the growth of tumours formed by mutant BrafV600E mouse melanoma cells in an immunocompetent host requires their production of PGE2, which suppresses immunity and fuels tumour-promoting inflammation. Genetic ablation of cyclooxygenases (COX) or prostaglandin E synthases in BrafV600E mouse melanoma cells, as well as in NrasG12D melanoma or in breast or colorectal cancer cells, renders them susceptible to immune control and provokes a shift in the tumour inflammatory profile toward classic anti-cancer immune pathways.
Furthermore, proof-of-concept pre-clinical data demonstrate that inhibition of COX synergises with anti-PD-1 blockade in inducing tumour eradication, implying that COX inhibitors could be useful adjuvants for immune-based therapies in cancer patients.
The mechanisms by which melanoma and other cancer cells evade anti-tumor immunity remain incompletely understood. This study shows that the growth of tumours formed by mutant BrafV600E mouse melanoma cells in an immunocompetent host requires their production of PGE2, which suppresses immunity and fuels tumour-promoting inflammation. Genetic ablation of cyclooxygenases (COX) or prostaglandin E synthases in BrafV600E mouse melanoma cells, as well as in NrasG12D melanoma or in breast or colorectal cancer cells, renders them susceptible to immune control and provokes a shift in the tumour inflammatory profile toward classic anti-cancer immune pathways.
Furthermore, proof-of-concept pre-clinical data demonstrate that inhibition of COX synergises with anti-PD-1 blockade in inducing tumour eradication, implying that COX inhibitors could be useful adjuvants for immune-based therapies in cancer patients.
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“We are so pleased to have received the funding to enable us to test our hypothesis in the lab. If we can create a new medicine that can precisely target a specific type of cell within the tumour, and restore anti-cancer immune responses, this will be a game-changer for oesophageal cancer patients “
Sara Valpione
Former Institute Clinical Fellow and now Clinician in Residence within the CRUK National Biomarker Centre
“My charity bake sales – known as “David’s Great British Bake Off” – are always a hit, home baked products taste so much better than shop bought and are greatly appreciated by staff!”
David Jenkins
Purchasing Officer
“We’ve seen some remarkable responses, with an improvement for some patients within days. This is an early phase trial so there’s a lot more work to do. But the data we have so far is very encouraging and could help many thousands of people in the future”
Tim Somervaille
Senior Group Leader
“It is a pleasure to introduce my team who work to deliver our research goals. We work in a friendly and collaborative environment, supporting each other’s projects. “
Amaya Virós
CRUK Advanced Clinician Scientist Fellow
“We are so pleased to have received the funding to enable us to test our hypothesis in the lab. If we can create a new medicine that can precisely target a specific type of cell within the tumour, and restore anti-cancer immune responses, this will be a game-changer for oesophageal cancer patients “
Sara Valpione
Former Institute Clinical Fellow and now Clinician in Residence within the CRUK National Biomarker Centre
“My charity bake sales – known as “David’s Great British Bake Off” – are always a hit, home baked products taste so much better than shop bought and are greatly appreciated by staff!”
David Jenkins
Purchasing Officer
“We’ve seen some remarkable responses, with an improvement for some patients within days. This is an early phase trial so there’s a lot more work to do. But the data we have so far is very encouraging and could help many thousands of people in the future”
Tim Somervaille
Senior Group Leader
“It is a pleasure to introduce my team who work to deliver our research goals. We work in a friendly and collaborative environment, supporting each other’s projects. “
Amaya Virós
CRUK Advanced Clinician Scientist Fellow