Cohort Analysis of ADAM8 Expression in the PDAC Tumor Stroma

Pancreatic ductal adenocarcinoma (PDAC) is a cancer type with one of the highest mortalities. The metalloprotease-disintegrin ADAM8 is highly expressed in pancreatic cancer cells and is correlated with an unfavorable patient prognosis. However, no information is available on ADAM8 expression in cells of the tumor microenvironment. We used immunohistochemistry (IHC) to describe the stromal cell types expressing ADAM8 in PDAC patients using a cohort of 72 PDAC patients. We found ADAM8 expressed significantly in macrophages (6%), natural killer cells (40%), and neutrophils (63%), which showed the highest percentage of ADAM8 expressing stromal cells. We quantified the amount of ADAM8⁺ neutrophils in post-capillary venules in PDAC sections by IHC. Notably, the amount of ADAM8⁺ neutrophils could be correlated with post-operative patient survival times. In contrast, neither the total neutrophil count in peripheral blood nor the neutrophil-to-lymphocyte ratio showed a comparable correlation. We conclude from our data that ADAM8 is, in addition to high expression levels in tumor cells, present in tumor-associated stromal macrophages, NK cells, and neutrophils and, in addition to functional implications, the ADAM8-expressing neutrophil density in post-capillary venules is a diagnostic parameter for PDAC patients when the numbers of ADAM8⁺ neutrophils are quantified.