In a new study, researchers have used artificial intelligence (AI) to reveal an aggressive form of pancreatic cancer that is more likely to respond to immunotherapy, in the most extensive analysis of the immune landscape of these tumors to date.
They found that a particularly aggressive type of these tumors can evade immune attack by hijacking the immune system’s response to viral infections, and reveals possible targets for immunotherapy for this rare, hard-to-treat form of pancreatic cancer.
Next, the researchers plan to translate their findings into new clinical trials to test the possible benefit of immunotherapies in those patients most likely to respond.
The research was conducted by a team at The Institute of Cancer Research, London, and elsewhere.
Pancreatic neuroendocrine cancer starts in cells that produce hormones such as insulin.
Once it spreads, only one in four people will survive for more than five years, and new treatment options are desperately needed.
In the study, the team used AI and genetic analysis to study 207 tumor samples from patients with pancreatic neuroendocrine tumors 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 tumors, saw changes in activity of 74 immune-related genes, compared with changes in only 12 immune system genes in the more benign insulinoma-like tumors.
In addition, 83% of aggressive, metastatic-like tumors 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 tumor.
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 tumors, which tend to be larger in size.
The researchers believe that by hijacking the damage response through TLR3—which helps flag tumor cells to the immune system—cancer cells can escape from the immune system, leading to the tumor’s ability to grow and evolve.
Importantly, the team also studied the presence of known targets for existing immunotherapies in all four kinds of pancreatic neuroendocrine tumors.
They found that the most aggressive type had the highest levels of an immune marker known as PD-L1, which suggests they can be targeted with immunotherapies designed to take the brakes off the immune system so it can attack tumor cells, known as checkpoint inhibitors.
Immunotherapy treatments have been shown to work very well in some tumor types—but they don’t work for everyone and have only shown modest benefits in this form of pancreatic cancer, so it is important to be able to identify the patients who are most likely to benefit from immunotherapy.
The researchers now hope their results will lead to clinical trials to test the benefit of immunotherapies, either alone or in combination with other treatments, for patients with the metastatic-like form of pancreatic neuroendocrine tumors.
The study is published in Gut.
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