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T-cell landscape mapping identifies new targets for pancreatic cancer immunotherapy

12/04/2021

Oxford researchers have used analysis of T-cell populations to identify new therapeutic opportunities in pancreatic cancer patients.

Pancreatic cancer has one of the worst prognoses of any cancer, with pancreatic ductal adenocarcinoma (PDAC) patients having an average survival rate of 7 percent. 

T-cells (the lymphocytes that play a wide range of roles in shaping the body's immune response to cancer) are known to be less active in pancreas tumours. So far, checkpoint therapy trials, a type of immune therapy that targets T-cells and have curative properties on other cancer types, have had minimal effect on pancreatic cancer with a response rate of only 5-10 percent. 

Furthermore there has been no lasting impact on a patient's survival chance and current approved checkpoint therapies are focused on only targeting two T-cell checkpoints, known as PD-1 and CTLA4. 

To better understand why checkpoint treatment has had a minimal impact on pancreatic cancer, and how to improve their efficacy, there is a need to understand the specific sub-populations of T-cells that are involved in pancreatic cancer. 

Even though we know T-cells exist in the microenvironment of pancreatic cancer, little is known about why they are less active. There is also a need to identify new checkpoint therapy targets, beyond the two currently used, so that new, more impactful drugs may be developed.

A new study from researchers in the PancrImmune network at the University of Oxford, has characterised the immune landscape, and specifically the different T-cells, in pancreatic cancer patients, in the hope of understanding the features to aid drug development and novel therapeutics for this disease. 

This is the first comprehensive characterisations of T-cells in primary human pancreatic ductal adenocarcinoma.

The team, which includes researchers from the University of Oxford and Oxford University Hospitals NHS Foundation Trust, looked at 32,000 T-cells from eight cancer patients, to see if there were any unique T-cell subtypes in the tumour microenvironment.

First, this data confirmed that the microenvironment of pancreatic cancer is extremely suppressive and could be a major driver of poor prognosis. Secondly, they identified important genetic components of these T-cell subtypes that may be driving this immunosuppression, which could be potential targets for future immunotherapy drugs.

The next step in this research is to take the newly-identified immunotherapy target and begin clinical experiments using targeted immunotherapy drugs. This may eventually lead to clinical trials to test these drugs in patients.

Mapping the immune landscape in PDAC patients is a huge step in pancreatic cancer research, as PDAC tumours represent 50 percent of all pancreatic cancer diagnoses. The new targets identified in this study have the potential to generate novel drugs that could benefit a large range of patients.