Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome

Immunotherapies targeting aspects of T cell functionality are efficacious in many solid tumors, but pancreatic ductal adenocarcinoma (PDAC) remains refractory to these treatments. Deeper understanding of the PDAC immune ecosystem is needed to identify additional therapeutic targets and predictive biomarkers for therapeutic response and resistance monitoring. To address these needs, we quantitatively evaluated leukocyte contexture in 135 human PDACs at single-cell resolution by profiling density and spatial distribution of myeloid and lymphoid cells within histopathologically-defined regions of surgical resections from treatment-naive and presurgically (neoadjuvant)-treated patients and biopsies from metastatic PDAC. Resultant data establishes an immune atlas of PDAC heterogeneity, identifies leukocyte features correlating with clinical outcomes, and through an in silico study, provides guidance for use of PDAC tissue microarrays to optimally measure intratumoral immune heterogeneity. Atlas data has direct applicability as a reference for evaluating immune responses to investigational neoadjuvant PDAC therapeutics where pre-therapy baseline specimens are not available.