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Int J Cancer. 2019 Feb 5. doi: 10.1002/ijc.32186. [Epub ahead of print]

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

Author information

1
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
2
Centre for Computational Biology, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.
3
GROW School for Oncology and Developmental Biology, Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands.
4
Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
5
Department of Oncology, University of Oxford, Oxford, United Kingdom.
6
Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
7
Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom.
8
Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.
9
Department of Pathology, New York University School of Medicine, New York, NY.

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.

KEYWORDS:

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

PMID:
30720864
DOI:
10.1002/ijc.32186

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