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Aspirin boosts cancer immunotherapy, study shows

Researchers reveal breakthrough discovery

Jo Carlowe

Friday, 04 September 2015

Aspirin may increase the power of immunotherapies used to fight cancer, researchers have revealed this week.

Professor Caetano Reis e Sousa and his Cancer Research UK-funded team at The Francis Crick Institute, have announced their breakthrough finding* in the journal Cell

The researcher team were interested in the chemical signal prostaglandin E2, exploring its role in suppressing T cells.

Prostaglandin E2 is made by molecular machines in cyclo-oxygenase 1 and (COX-1 and COX-2). Existing evidence suggests levels of COX are unusually high in several types of cancer, including bowel, breast and lung. So Professor Reis e Sousa and his team set about investigating whether prostaglandin E2 or COX-1 and 2 could be possible targets for treating cancer.

Their latest research focuses on lab-grown melanoma skin cancer cells, originally taken from mice that were genetically prone to developing the disease, due to a fault in the BRAF gene.

Using the new genetic engineering technique CRISPR, the researchers deliberately ‘edited out’ the COX-1 and COX-2 genes in the melanoma cells, meaning they could no longer make prostaglandin E2. And – just as they suspected – the cancer cells lost their ability to damp down the immune response.

Next, the researchers compared mice transplanted with ‘normal’ skin cancer cells to mice whose melanoma cells lacked COX-1 and -2 genes, and they spotted two important things. Firstly, animals with tumours lacking COX-1 and -2 had a much stronger immune reaction to the cancer cells. And secondly, this reaction meant that the tumours with missing COX genes could now be attacked by immune cells, unlike cancers with normal COX genes.

The scientists saw a similar pattern when they repeated the experiments with bowel and breast cancer cells, implicating prostaglandin E2 in the growth of these types of cancer too.

Professor Reis e Sousa wondered whether aspirin might be able to mimic the effects of knocking out the COX genes, reducing prostaglandin E2 levels and helping to drive a stronger immune response against the mice’s tumours. Just as they’d seen in their genetic engineering experiments.

To test this idea, the researchers added aspirin to the drinking water of mice transplanted with melanoma cells. By itself, the drug had no effect but when combined with a checkpoint inhibitor, the mice given aspirin along with the immunotherapy drug got rid of their tumours much more quickly than those receiving immunotherapy alone. Moreover, the animals developed a strong immune ‘memory’, and their immune cells recognised and immediately destroyed the same type of cancer cells, even months after the first experiment.

The scientists saw the same immunotherapy-boosting power of aspirin when mice were transplanted with bowel cancer cells: even though the immunotherapy didn’t have much effect by itself, the tumours shrank significantly in around a third of the animals treated with the combination.

More work is now needed to prove whether aspirin has this effect in human tumours, as well as clinical trials to test the effectiveness and safety of the combined treatment.

* Caetano Reis e Sousa, et al. Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity. Cell, September 2015. doi: http://dx.doi.org/10.1016/j.cell.2015.08.015

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