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Immuno-phenotypes of Pancreatic Ductal Adenocarcinoma: Metaanalysis of transcriptional subtypes

View ORCID ProfileInes de Santiago, View ORCID ProfileChristopher Yau, Mark Middleton, View ORCID ProfileMichael Dustin, View ORCID ProfileFlorian Markowetz, View ORCID ProfileShivan Sivakumar
doi: https://doi.org/10.1101/198903
Ines de Santiago
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
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  • For correspondence: ines.desantiago@cruk.cam.ac.uk shivan.sivakumar@oncology.ox.ac.uk
Christopher Yau
2Centre for Computational Biology, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
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Mark Middleton
3Department of Oncology, University of Oxford, Oxford, UK
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Michael Dustin
4Kennedy Institute of Rheumatology, University of Oxford
5Department of Pathology, New York University School of Medicine, New York, USA
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Florian Markowetz
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
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Shivan Sivakumar
3Department of Oncology, University of Oxford, Oxford, UK
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  • For correspondence: ines.desantiago@cruk.cam.ac.uk shivan.sivakumar@oncology.ox.ac.uk
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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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted October 05, 2017.
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Immuno-phenotypes of Pancreatic Ductal Adenocarcinoma: Metaanalysis of transcriptional subtypes
Ines de Santiago, Christopher Yau, Mark Middleton, Michael Dustin, Florian Markowetz, Shivan Sivakumar
bioRxiv 198903; doi: https://doi.org/10.1101/198903
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Immuno-phenotypes of Pancreatic Ductal Adenocarcinoma: Metaanalysis of transcriptional subtypes
Ines de Santiago, Christopher Yau, Mark Middleton, Michael Dustin, Florian Markowetz, Shivan Sivakumar
bioRxiv 198903; doi: https://doi.org/10.1101/198903

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