Cytometric Atlas of Combination Immunotherapy in Pancreatic Cancer: Blood-Based Signatures Reveal Vaccine and Checkpoint Inhibitor Responses

Abstract Combination vaccine and checkpoint inhibitor therapy has previously demonstrated immunologic responses in patients with pancreatic ductal adenocarcinoma (PDAC), although with limited efficacy. An urgent need to augment responses has warranted a deeper understanding of how each treatment modality contributes to the overall inflammatory response. Serial blood samples from PDAC patients treated with GVAX, CRS-207, anti-CTLA-4, and/or anti-PD-1 therapies were profiled using two mass cytometry panels. Generating 260 cytometric profiles from 64 unique patients allowed us to create an annotated PDAC immunotherapy atlas. Analysis of this atlas revealed that while GVAX alone did not significantly alter T-cell relative frequencies, it induced T-cell activation and upregulated checkpoint expression. Adding anti-PD-1 blockade to GVAX further enhanced T-cell activation, whereas adding anti-CTLA-4 distinctly enhanced memory formation. Vaccine-mediated effects were similar, but GVAX promoted plasmacytoid dendritic cells more than CRS-207. Derived phenotypic patterns could also be projected onto tumor imaging data, underscoring the potential for discoveries relating treatment-induced peripheral signatures to changes in the tumor microenvironment.