Pancreatic ductal
adenocarcinoma (PDA) is usually unresponsive to immunotherapeutic approaches. However,
tertiary lymphoid structures (TLS) are associated with favorable patient outcomes in PDA. A better understanding of the B cell infiltrate and biological features of TLS formation is needed to further explore their potential and improve patient management. We analyzed
tumor tissues (n = 55) and corresponding blood samples (n = 51) from PDA patients by systematical immunohistochemistry and multiplex
cytokine measurements. The tissue was compartmentalized in "
tumor" and "stroma" and separately examined. Clinical patient information was used to perform survival analyses. We found that the mere number of B cells is not associated with patient survival, but formation of TLS in the peritumoral stroma is a prognostic favorable marker in PDA patients. TLS-positive tissues show a higher density of CD8+ T cells and CD20+ B cells and a higher
IL2 level in the peritumoral stroma than tissues without TLS. Compartmental assessment shows that gradients of
IL2 expression differ with regard to TLS formation: TLS presence is associated with higher
IL2 levels in the stromal than in the tumoral compartment, while no difference is seen in patients without TLS. Focusing on the stroma-to-serum gradient, only patients without TLS show significantly higher
IL2 levels in the serum than in stroma. Finally, low circulatory
IL2 levels are associated with local TLS formation. Our findings highlight that TLS are prognostic favorable and associated with antitumoral features in the microenvironment of PDA. Also, we propose easily accessible serum
IL2 levels as a potential marker for TLS prediction.