Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas and has one of the highest mortality rates of any cancer type with a 5-year survival rate of < 5% and median overall survival of typically six months from diagnosis. Recent transcriptional studies of PDAC have provided several competing stratifications of the disease. However, the development of therapeutic strategies will depend on a unique and coherent classification of PDAC. Here, we use an integrative meta-analysis of four different PDAC gene expression studies to derive the consensus PDAC classification. Despite the fact that immunotherapies have yet to have an impact in treatment of PDAC, the gene expression signatures that stratify PDAC across studies are immunologic. We define these as “adaptive”, “innate” and “immune-exclusion” immunologic signatures, which are prognostic across independent cohorts. An appreciation of the immune composition of PDAC with prognostic significance is an opportunity to understand distinct immune escape mechanisms in development of the disease and design novel immune-oncology therapeutic strategies to overcome current barriers.
Footnotes
Conflicts of Interest: MM reports personal fees from Amgen, grants and personal fees from Roche, grants from Astrazeneca, grants and personal fees from GSK, personal fees and other from Novartis, other from Astellas (was OSI), other from Millenium, non-financial support and other from Immunocore, personal fees and other from BMS, other from Vertex, personal fees and other from Eisai, other from Pfizer, personal fees, non-financial support and other from Merck, personal fees and other from Rigontec, personal fees from Cytomx, other from Regeneron, other from TCBiopharma, personal fees from Bioline, personal fees and other from Array Biopharma, other from Replimune, personal fees from Valo Therapeutics, outside the submitted work.
MD reports fees as a consultant on the Scientific Advisory Board of Adaptimmune.
The other authors do not report any conflicts of interest.