Unlocking the potential of immunotherapy to treat pancreatic cancer

A new form of treatment called immunotherapy has revolutionised the treatment of some forms of cancer. Here, Research Communications Volunteer Anna Sanders takes a look at how immunotherapy works, and the research that is taking place to investigate it’s potential as a new treatment for pancreatic cancer.

Summary

Your immune system protects you from infections and disease and can also play a role in detecting and destroying cancer cells. However, it does not always destroy cancer effectively. Researchers are now developing treatments called immunotherapies that help the immune system fight cancer more effectively.

While immunotherapy has transformed treatment for some cancers, it has been much more challenging to use against pancreatic cancer. Researchers, including those funded by Pancreatic Cancer UK, are working to overcome these challenges and develop new treatment options for the future.

What is our immune system and how does it work?

The immune system is our body’s natural defence against infection and disease. It constantly patrols the body looking for anything unusual and protects us from harmful bacteria, viruses and other threats. It can also recognise and remove damaged or abnormal cells, including cells that may become cancerous. These often carry special markers called antigens, which act like flags so that they can be easily identified by immune cells.

Two important types of cells in the immune system are B cells and T cells.

• B cells produce antibodies, which are tiny proteins that recognise and attach to invaders such as bacteria and viruses, marking them for destruction by other immune cells.
• T cells directly attack infected or abnormal cells rather than producing antibodies. Some T cells destroy cells that have become cancerous, while others activate the wider immune response by activating other immune cells.

After a threat has been removed, some B cells and T cells remain in the body as memory cells. Remembering threats ‘seen’ before helps the body respond more quickly if the same danger returns in the future.

What is immunotherapy and how does work?

Immunotherapy is an emerging treatment that helps the immune system detect and fight cancer more effectively. It includes the following types of treatments:

• Checkpoint inhibitors – T cells have natural control switches, called checkpoints, which prevent the immune system attacking its own cells and organs. However, pancreatic cancer can stop T cells working effectively. Drugs known as checkpoint inhibitors work by releasing these brakes, allowing T cells to recognise and destroy cancer cells again.
• CAR-T cell therapy involves collecting a patient’s T cells and genetically modifying them in a laboratory so they can better recognise cancer cells. The modified cells are then returned to the patient to seek out and destroy cancer.
• Cancer vaccines train the immune system to recognise specific antigens present on cancer cells, helping it target tumours while avoiding killing healthy tissue.

Immunotherapy has dramatically improved outcomes for some cancers, such as melanoma (a type of skin cancer) and certain blood cancers. However, it has so far had limited success in pancreatic cancer.

What are the challenges around using immunotherapy to treat pancreatic cancer?

Because pancreatic cancers are very good at finding ways to avoid detection and escape immune attacks, they are extremely difficult to treat. One major challenge is the tumour microenvironment (TME). This is the dense barrier surrounding the tumour, containing scar tissue, blood vessels, immune cells and other supporting cells. Pancreatic cancer cells hide behind it, making it difficult for immune cells and drugs to reach and attack them. Alternatively, when T cells finally enter the tumour, they may be suppressed and unable to function effectively.

Pancreatic cancer cells also tend to have fewer obvious markers for the immune system to recognise. This makes it harder for T cells to identify them and for treatments such as CAR-T cell therapy to be successful.

Because of these challenges, immunotherapy alone is often less effective. Researchers are therefore exploring combination approaches such as pairing immunotherapy with chemotherapy or radiotherapy or targeting the TME itself. Scientists hope that by disrupting or modifying this protective environment, it may become possible to improve immune cell access and make treatment more effective.

Is immunotherapy currently being used to treat pancreatic cancer in the UK?

Immunotherapy for pancreatic cancer remains experimental and is mainly available through clinical trials.

For most people with pancreatic cancer, experimental immunotherapy has not yet shown promising results, although it may benefit a small number of patients whose tumours have specific genetic features. If appropriate and eligible, patients can access some genetic testing via the NHS. You can speak to your medical team about whether this could be an option for you.

What is Pancreatic Cancer UK doing to support immunotherapy for pancreatic cancer?

Pancreatic Cancer UK’s Grand Challenge award previously helped demonstrate that immunotherapy could potentially work in treating pancreatic cancer.

Through this award, researchers:

• identified new markers on pancreatic cancer cells that could help the immune system recognise tumours more effectively
• developed specialised CAR-T cells that slowed tumour growth and improved survival in mice
• showed that combining immunotherapy with tumour-targeting viruses could help immune cells reach tumours protected by dense scar tissue

Today, we are continuing to support this promising area of research. Current projects focused on immunotherapy include the following:

• At the University of Oxford, Dr Peter Wan is developing new antibody-based immunotherapies designed to help immune cells break through the tumour’s protective environment.
• Also in Oxford, Dr Keaton Jones and Dr Michael Gray are investigating whether a technique called focused ultrasound could stimulate the immune system and improve the effectiveness of immunotherapy.
• In Manchester, Professor Claus Jorgensen is studying the scar tissue surrounding pancreatic tumours to better understand how it helps cancer evade the immune system and resist treatment.

These projects are addressing some of the key barriers that have limited the success of immunotherapy in pancreatic cancer so far.

Continued research is helping to bring us closer to a future where immunotherapy could play a much greater role in treating pancreatic cancer.