Over the last decade, treatment of cancer has been revolutionised by the tremendous success of cancer immunotherapies, i.e. drugs aiming at boosting the patient’s own immune system against its tumour. Such treatments have led to improved survival and long-term remission in a substantial proportion of treated patients, and have now become the standard of care in specific tumour types, such as melanoma. However, not all types of tumours are sensitive to immunotherapies. One such example is pancreatic cancer, among which pancreatic adenocarcinoma (PDAC) represents the most common subtype.
PDAC is one of the most aggressive cancer types, with a five-year survival rate of less than 5%. Among PDAC risk factors, pancreatitis emerges as a critical player in tumour development, as evidenced from both human data and pre-clinical mouse models. Despite intensive research, no improvement in this five-year survival rate has been achieved over the past 4 decades, illustrating how cutting-edge research in this field is crucial to tackle such an unmet clinical need.
An extensive amount of work has been achieved at defining critical signalling pathways for pancreatic cancer cell survival as well as the mutational landscape in pancreatic tumours. However, our understanding of the interaction between immune cells and the exocrine pancreas – healthy, inflamed or tumoral – has just begun to be explored.
In this work we set out to test the hypothesis that a novel subset of tissue-resident immune cells termed “type-2 innate lymphoid cells”, or ILC2s, influence the epithelial cell niche in the pancreas by locally regulating inflammation. Using state-of-the art mouse models of pancreatitis and pancreatic tumors, our results reveal distinct and previously unappreciated roles for ILC2s-driven mechanisms in regulating pancreatic epithelial cells upon inflammation and tumorigenesis.
