B cells in pancreatic cancer stroma

Abstract

Pancreatic cancer is a disease with high unmet clinical need. Pancreatic cancer is also characterised by an intense fibrotic stroma, which harbours many immune cells. Studies in both human and animal models have demonstrated that the immune system plays a crucial role in modulating tumour onset and progression. In human pancreatic ductal adenocarcinoma, high B-cell infiltration correlates with better patient survival. Hence, B cells have received recent interest in pancreatic cancer as potential therapeutic targets. However, the data on the role of B cells in murine models is unclear as it is dependent on the pancreatic cancer model used to study. Nevertheless, it appears that B cells do organise along with other immune cells such as a network of follicular dendritic cells (DCs), surrounded by T cells and DCs to form tertiary lymphoid structures (TLS). TLS are increasingly recognised as sites for antigen presentation, T-cell activation, B-cell maturation and differentiation in plasma cells. In this review we dissect the role of B cells and provide directions for future studies to harness the role of B cells in treatment of human pancreatic cancer.

Keywords: B cells; Pancreatic cancer; Cancer immunology; Tertiary lymphoid structures; Anti-tumour immunoglobulins; Plasma cells

Core Tip: The role of B cells in pancreatic ductal adenocarcinoma tumorigenesis is controversial. Human studies show clusters of B cells, interacting with other immune cells, forming active sites of the immune response, called tertiary lymphoid structures. In vitro experiments and in vivo studies using B-cell deficient mice suggest the role of an immuno-suppressive B cell phenotype to induce tumour-progression. These discordant findings highlight the need of further studies using better murine models to recapitulate pancreatic cancer and its immune infiltrate.