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

Int J Cancer. 2019 Aug 15;145(4):1125-1137. doi: 10.1002/ijc.32186. Epub 2019 Mar 18.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cluster Analysis
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Immunophenotyping / methods
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Transcription, Genetic / genetics*
  • Transcriptome / genetics*

Supplementary concepts

  • Pancreatic Carcinoma