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 (FAS) and CD45RA (PTPRC) 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.