Scientists tear down pancreatic cancer's defences

Cancer Research UK

Cancer Research UK scientists, in collaboration with scientists from AstraZeneca’s Oncology Innovative Medicines Unit, have shown how an experimental drug breaks down pancreatic cancer’s defences, allowing immune cells to sweep in and attack the tumour.

"This might unleash a powerful weapon against this deadly disease where we are desperately in need of new treatments." - Professor Peter Johnson 

The new study, published in Cancer Cell*, discovered that a protein called CXCR2 helps guard the tumour, controlling how the immune system responds to pancreatic cancer**.

Pancreatic cancer has a complex relationship with the immune system. In its early stages the disease must evade the immune surveillance system but once past this initial attack, pancreatic cancer hijacks parts of the immune system to aid its progression.

Studying pancreatic cancer samples from patients and in mice, the researchers showed that CXCR2 plays a key part in this dual role, ultimately helping pancreatic cancers develop and spread around the body.

Using an experimental drug that blocks CXCR2, the researchers stopped the tumour spreading. When this blocking process was used with drugs that boost the immune system they saw an influx of T-cells into the tumour that were primed to attack the disease, improving the survival of mice.

Dr Jennifer Morton, lead researcher based at the Beatson Institute in Glasgow, said: “One of the most striking effects of blocking CXCR2 was the rush of T-cells into the tumour. This influx may be responsible for the improved success of gemcitabine and also made the tumours more sensitive to immunotherapy. Future approaches to using immunotherapy for pancreatic cancer suggest that using a CXCR2 blocking drug may be most effective to prime the tumour.” 

Professor Peter Johnson, Cancer Research UK’s chief clinician, said: “Pancreatic cancer has proven hard to treat with Immunotherapy, because it is often shielded by cells that fend off the immune system.  This study suggests that we could overcome this by using immunotherapies with drugs that target the CXCR2 protein, letting the immune cells in to attack the cancer.  This might unleash a powerful weapon against this deadly disease where we are desperately in need of new treatments. 

“Pancreatic cancer remains an incredibly hard cancer to treat, with just three per cent of patients surviving for five years. To turn this around Cancer Research UK is bringing together the research community to tackle this disease. Research like this opens exciting new avenues in both understanding more about understanding and treating the disease.”

ENDS

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Notes to Editor

*Steele, C., et al. CXCR2 inhibition profoundly suppresses metastases ad augments immunotherapy in pancreatic ductal adenocarcinoma (Cancer Cell 2016)

**The insights from this work are being explored clinically with AZD5069, AstraZeneca’s CXCR2 inhibitor (previously studied in the clinic for COPD and asthma), being evaluated for squamous cell carcinoma of the head and neck.