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Immunophenotypes of pancreatic ductal adenocarcinoma: Meta-analysis of transcriptional subtypes.

Published version
Peer-reviewed

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Type

Article

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Authors

de Santiago, Ines 
Yau, Christopher 
Heij, Lara 
Middleton, Mark R 

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%. Recent studies of PDAC have provided several transcriptomic classifications based on separate analyses of individual patient cohorts. There is a need to provide a unified transcriptomic PDAC classification driven by therapeutically relevant biologic rationale to inform future treatment strategies. Here, we used an integrative meta-analysis of 353 patients from four different studies to derive a PDAC classification based on immunologic parameters. This consensus clustering approach indicated transcriptomic signatures based on immune infiltrate classified as adaptive, innate and immune-exclusion subtypes. This reveals the existence of microenvironmental interpatient heterogeneity within PDAC and could serve to drive novel therapeutic strategies in PDAC including immune modulation approaches to treating this disease.

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Keywords

T cells, adaptive immunity, innate immunity, pancreatic cancer, subtypes, tumour microenvironment

Journal Title

International Journal of Cancer

Conference Name

Journal ISSN

1097-0215
1097-0215

Volume Title

Publisher

John Wiley & Sons Inc.
Sponsorship
Cancer Research UK (C14303/A17197)
This study was supported by the NIHR Oxford Biomedical Research Centre. CY is supported by a UK Medical Research Council Research Grant (MR/P02646X/1). MLD is funded by Wellcome Trust grant 100262Z/12/Z. SS is funded by a NIHR Academic Clinical Lecturership.