Immunogenicity of SEREX-identified antigens and disease outcome in pancreatic cancer

摘要: Despite spontaneous or vaccination-induced immune responses, pancreatic cancer remains one of the most deadly immunotherapy-resistant malignancies. We sought to comprehend spectrum tumor-associated antigens (pTAAs) and assess clinical relevance their immunogenicity. An autologous SEREX-based screening a cDNA library constructed from T3N0M0/GIII specimen belonging long-term survivor (36 months) revealed 18 immunogenic pTAA. RT-PCR analysis displayed broad distribution identified among normal human tissues. PNLIPRP2 MIA demonstrated distinct cancer-specific patterns. ELISA-based sera for corresponding autoantibodies that although significantly increased, immunogenicity these molecules was not common feature in cancer. QRT-PCR immunohistochemistry characterized as robust acinar cell-specific marker whose decreased expression mirrored disappearance parenchyma diseased organ, but related presence autoantibodies. Analyses MIA—known be preferentially expressed malignant cells—surprisingly an inverse correlation between intratumoral gene emergence MIAhigh patients were autoantibody-negative had shorter median survival when compared with autoantibody-positive MIAlow (12 vs. 34 months). The observed pTAA comprised associated acinar, stromal structures, thus presenting novel targets tumor therapies well approaches based on bystander effects. Applying concept immunoediting interpret relationships expression, antitumor outcome might better discriminate past ongoing consequently enabling prognostic stratification individual adjustment immunotherapy.