Non-tumour cells in pancreatic cancer may reduce the effectiveness of the body’s natural immune response

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. It is highly aggressive due to its late presentation and poor response to therapy, with five-year survival rates remaining around 10%. PDAC is set to become the second leading cause of cancer-related deaths in the US by 2040, and therefore finding improved treatments for this disease is becoming increasingly critical. 

A study carried out by Rachel Fincham, a doctoral student under the guidance of Hemant Kocher, Professor of Liver and Pancreas Surgery at Queen Mary University of London and Barts Health NHS Trust, has found that treatment targeting the non-tumour, ‘stromal’ cells in pancreatic cancer with an aim of reverting them to a resting state can improve patient outcome. The study investigated the potential interactions between these stromal cells (also known as pancreatic stellate cells or cancer associated fibroblasts) and a specific type of immune cells called natural killer (NK) cells. 

Results from cell line experiments, mouse models, and samples from patient tissues, perform in London and Singapore (under guidance of Dr Joe Yeong) showed that exposing NK cells to resting stromal cells significantly decreased their capacity to attack pancreatic cancer cells. The study also demonstrated significant bi-directional interaction between NK and stromal cells and found that co-culturing these cell types significantly, and reciprocally, modulated their phenotype and altered their biological pathways. 

In mouse models, the study also found that standard therapeutic regimes caused striking differences in the spatial distribution of NK cells. Importantly, assessment of patient samples showed that having greater distance between NK cells and the cancer’s stromal cells was associated with people who had survived this type of cancer for longer.  

Professor Kocher said: "Our work provides novel insights into the relationship between the immune system and stromal cells in pancreatic cancer. Our exciting findings highlight the prognostic implications of natural killer-stromal cell proximity in pancreatic cancer, and we suggest its potential use as a tool for patient stratification for diagnosis, prognosis and treatment."

This research was conducted by researchers from Barts Cancer Institute, the Institute of Molecular and Cell Biology (IMCB), Singapore, the Centre for Quantitative Medicine, Duke-National University of Singapore (NUS) Medical School,  the Department of Anatomical Pathology, Singapore General Hospital, the Cancer Science Institute of Singapore, National University of Singapore,  and the Barts and the London Hepato-Pancreato-Biliary (HPB) Centre, The Royal London Hospital, Barts Health National Health Service Trust. Funding was provided by Barts Charity and A*STAR Research Attachment Programme (ARAP) PhD studentship. The Pancreatic Cancer Research Fund Tissue Bank is funded by Pancreatic Cancer Research Fund.