The immunological landscape in pancreatic ductal adenocarcinoma and overcoming resistance to immunotherapy.

Marc Hilmi, Matthieu Delaye, Milena Muzzolini, Rémy Nicolle, Jérôme Cros, Pascal Hammel, Victoire Cardot-Ruffino, Cindy Neuzillet

Journal: The lancet. Gastroenterology & hepatology 2023;8(12):1129-1142

PMID: 37866368

Full Text on Elsevier Science View on PubMed

Abstract

Pancreatic ductal adenocarcinoma is associated with a poor prognosis and there are few treatment options. The development of immunotherapy in pancreatic ductal adenocarcinoma has been difficult, and immune checkpoint inhibitors are only effective in a very small subset of patients. Most obstacles for treatment have been related to intertumoural and intratumoural heterogeneity, the composition of tumour stroma, and crosstalk with cancer cells. Improved molecular characterisation of pancreatic ductal adenocarcinoma and a better understanding of its microenvironment have paved the way for novel immunotherapy strategies, including the identification of predictive biomarkers, the development of rational combinations to optimise effectiveness, and the targeting of new mechanisms. Future immunotherapy strategies should consider individual characteristics to move beyond the traditional immune targets and circumvent the resistance to therapies that have been developed so far.

Address: Gastrointestinal Oncology, Medical Oncology Department, Institut Curie, Université Versailles Saint-Quentin-Université Paris-Saclay, Saint-Cloud, France; Molecular Oncology, PSL Research University, CNRS, UMR 144, Institut Curie, Paris, France.; Digestive Surgery Department, Ambroise Paré Hospital, APHP, Université Versailles Saint-Quentin-Université Paris-Saclay, Boulogne Billancourt, France.; Université Paris Cité, Centre de Recherche sur l'Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, Paris, France.; Université Paris Cité, Pathology Department, Beaujon Hospital, FHU MOSAIC, AP-HP, Clichy, France.; Université Paris-Saclay, Department of Digestive and Medical Oncology, Paul-Brousse Hospital (APHP Sud), Villejuif, France.; Molecular Oncology, PSL Research University, CNRS, UMR 144, Institut Curie, Paris, France.; Gastrointestinal Oncology, Medical Oncology Department, Institut Curie, Université Versailles Saint-Quentin-Université Paris-Saclay, Saint-Cloud, France; Molecular Oncology, PSL Research University, CNRS, UMR 144, Institut Curie, Paris, France. Electronic address: [email protected].

DOI: 10.1016/S2468-1253(23)00207-8

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MeSH Terms: Humans, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal, Immunotherapy, Tumor Microenvironment