Rational: Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive disease associated with poor outcome. Most PDAC patients die within the first two years, and only a small subgroup of patients exceeds this survival rate. So far, factors and pathways underlying long-term survivorship in PDAC are unknown. In a previous study we showed that high CD8/FoxP3 ratio is associated with a favorable outcome. Therefore, we aimed to reveal the immune-related key players that drive the long-term survivorship in PDAC patients.
Methods: The immune-related gene expression profiles of 10 PDAC patients survived and free of recurrence for ≥ 5 years, was compared to 10 PDAC patients in whom recurrence and death occurred within 6 months after surgery. Samples were profiled using the PanCancer Immune Profiling Panel of nanoString technology. Subsequently, a subgroup of samples was measured by the GeoMx Digital Spatial Profiler (DSP) to determine the spatial location of the immune cells.
Results: The immune microenvironment in long-term survivors was altered differentially than that of the short-term survivors. B cells were found to be highly expressed in long-term survivors by gene expression profile. The presence of B cells was confirmed by performing a high-plex proteomic analysis with spatial resolution (GeoMx DSP). B cells infiltrated to the tumor stroma together with T cells and antigen presenting cells in long-term survivors.
Conclusion: This is the first comprehensive study that compares the expression and the spatial infiltration of immune cells in PDAC patients with different survival rates. Our data demonstrate that long-term survivorship of PDAC patients is influenced by the presence of B cells in the tumor microenvironment. The role of B cells in PDAC disease is controversial. However, our findings illustrate that B cells interact with other compartments of the immune system and drive long-term survivorship in PDAC patients.
Hosein Aziz1, Lawlaw Saida1, Jasper Dumas2,4, Andrew Stubbs2,3, Yunlei Li2,3, Casper van Eijck1,4 and Dana A. Mustafa2,4
1 Department of Surgery, 2 Department of Pathology, 3 Division of Clinical Bioinformatics, 4 The Tumor Immuno-Pathology (TIP) Laboratory, Erasmus University Medical Center, Rotterdam, the Netherlands.