Peripheral immune landscape in pancreatic ductal adenocarcinoma reveals expansion of effector states with disease progression

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy often diagnosed late due to the limited sensitivity and specificity of current modalities. To explore alternative strategies, we developed a high-dimensional immune profiling framework using 40-marker spectral flow cytometry to characterize peripheral blood from healthy individuals and treatment-naive PDAC patients across disease stages. This platform identified over 70 immune cell subsets and revealed stage-associated immune remodeling, including the expansion of effector and memory T cell populations, accompanied by reductions in naive and selected regulatory and innate compartments. By integrating multivariate, network, and machine learning analyses, we identified CD95 (<i>FAS</i>) and CD45RA (<i>PTPRC</i>) as candidate features that distinguish PDAC from healthy controls. Orthogonal evaluation using public single-cell and bulk transcriptomic datasets supported the remodeling of peripheral T cells, particularly the enrichment of CD4⁺ central memory T cells. Together, this study outlines a non-invasive immune profiling strategy with potential utility for classifying PDAC patients.