Immunotherapies could target aggressive pancreatic cancer, research indicates

Researchers have discovered that an aggressive form of pancreatic cancer 'hijacks' the immune system's response and therefore is more likely to respond to treatment with immunotherapy, raising hopes for new targets in the fight against the disease.

Scientists at The Institute of Cancer Research (ICR), London, and The Royal Marsden NHS Foundation Trust, working with colleagues at the University and Hospital Trust of Verona, Italy, used artificial intelligence (AI) and genetic analysis to study 207 tumour samples from patients with pancreatic neuroendocrine tumours for the levels of 600 immune-related genes.

Comparing four separate forms of the disease, they found that samples of the most aggressive form, known as metastases-like primary tumours, saw changes in activity of 74 immune-related genes, compared with changes in only 12 in the more benign insulinoma-like tumours.

The research, published in the journal Gut, revealed that 83% of aggressive, metastatic-like tumours contained particularly high levels of a gene called TLR3, part of a damage-alert system that mimics the infection response triggered by viruses, drawing immune cells to the tumour.

This damage response is related to a form of programmed cell death that occurs when there’s not enough oxygen – which can happen inside metastatic-like tumours, which tend to be larger in size.

Researchers believe that by hijacking the damage response through TLR3 cancer cells can escape from the immune system, leading to the tumour’s ability to grow and evolve.

The ICR team also looked at the presence of known targets for existing immunotherapies in all four kinds of pancreatic neuroendocrine tumours, and found that the most aggressive type had the highest levels PD-L1, which suggests they can be targeted with checkpoint inhibitors.

“Our new study offers an important basis from which to start developing new treatment strategies for a rare form of cancer, which starts in the hormone-producing cells of the pancreas,” noted Dr Anguraj Sadanandam, team leader in Systems and Precision Cancer Medicine at The ICR, London.

“We found that there is a complex interplay between cancer and immune cells in the most aggressive type of pancreatic neuroendocrine tumours, which suggests immunotherapy could work for patients with this form of the disease.

“Our findings could help to pick out those patients most likely to benefit from immunotherapy – and we’re keen to translate our work into clinical trials to test the benefit of different immunotherapeutic strategies to tackle this hard-to-treat form of pancreatic cancer.”