Stroma-nerve axis in pancreatic ductal adenocarcinoma: Bidirectional regulatory mechanisms and clinical translation hypothesis

Figure 2 Hypothetical stroma-nerve axis phenotypes in pancreatic ductal adenocarcinoma. Conceptual illustration of three stroma-nerve axis (SNA) activation patterns: SNA-I (nerve-dominant), with high nerve density, moderate stroma and sparse but suppressive immune infiltrates; SNA-II (stroma-dominant), with very dense cancer-associated fibroblast-rich stroma, low nerve prominence and an immune-excluded pattern; and SNA-III (balanced type), with intermediate nerve and stroma and a mixed immune infiltrate. The feature boxes summarize the relative levels of nerve activity, cancer-associated fibroblast/extracellular matrix and immune suppression/exclusion. These phenotypes are hypothesis-generating constructs and do not represent validated clinical subtypes. SNA: Stroma-nerve axis; CAF: Cancer-associated fibroblasts; ECM: Extracellular matrix.