Humoral immunoprofiling identifies novel biomarkers and an immune suppressive autoantibody phenotype at the site of disease in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous cancer, with minimal response to therapeutic intervention and with 85% of cases diagnosed at an advanced stage due to lack of early symptoms, highlighting the importance of understanding PDAC immunology in greater detail. Here, we applied an immunoproteomic approach to investigate autoantibody responses against cancer-testis and tumor-associated antigens in PDAC using a high-throughput multiplexed protein microarray platform, comparing humoral immune responses in serum and at the site of disease in order to shed new light on immune responses in the tumor microenvironment. We simultaneously quantified serum or tissue IgG and IgA antibody isotypes and subclasses in a cohort of PDAC, disease control and healthy patients, observing inter alia that subclass utilization in tumor tissue samples was predominantly immune suppressive IgG4 and inflammatory IgA2, contrasting with predominant IgG3 and IgA1 subclass utilization in matched sera and implying local autoantibody production at the site of disease in an immune-tolerant environment.