Cargando…

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

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 individ...

Descripción completa

Detalles Bibliográficos
Autores principales: de Santiago, Ines, Yau, Christopher, Heij, Lara, Middleton, Mark R., Markowetz, Florian, Grabsch, Heike I., Dustin, Michael L., Sivakumar, Shivan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767191/
https://www.ncbi.nlm.nih.gov/pubmed/30720864
http://dx.doi.org/10.1002/ijc.32186
_version_ 1783454859952914432
author de Santiago, Ines
Yau, Christopher
Heij, Lara
Middleton, Mark R.
Markowetz, Florian
Grabsch, Heike I.
Dustin, Michael L.
Sivakumar, Shivan
author_facet de Santiago, Ines
Yau, Christopher
Heij, Lara
Middleton, Mark R.
Markowetz, Florian
Grabsch, Heike I.
Dustin, Michael L.
Sivakumar, Shivan
author_sort de Santiago, Ines
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6767191
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley & Sons, Inc.
record_format MEDLINE/PubMed
spelling pubmed-67671912019-10-03 Immunophenotypes of pancreatic ductal adenocarcinoma: Meta‐analysis of transcriptional subtypes de Santiago, Ines Yau, Christopher Heij, Lara Middleton, Mark R. Markowetz, Florian Grabsch, Heike I. Dustin, Michael L. Sivakumar, Shivan Int J Cancer Tumor Immunology and Microenvironment 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. John Wiley & Sons, Inc. 2019-03-18 2019-08-15 /pmc/articles/PMC6767191/ /pubmed/30720864 http://dx.doi.org/10.1002/ijc.32186 Text en © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Tumor Immunology and Microenvironment
de Santiago, Ines
Yau, Christopher
Heij, Lara
Middleton, Mark R.
Markowetz, Florian
Grabsch, Heike I.
Dustin, Michael L.
Sivakumar, Shivan
Immunophenotypes of pancreatic ductal adenocarcinoma: Meta‐analysis of transcriptional subtypes
title Immunophenotypes of pancreatic ductal adenocarcinoma: Meta‐analysis of transcriptional subtypes
title_full Immunophenotypes of pancreatic ductal adenocarcinoma: Meta‐analysis of transcriptional subtypes
title_fullStr Immunophenotypes of pancreatic ductal adenocarcinoma: Meta‐analysis of transcriptional subtypes
title_full_unstemmed Immunophenotypes of pancreatic ductal adenocarcinoma: Meta‐analysis of transcriptional subtypes
title_short Immunophenotypes of pancreatic ductal adenocarcinoma: Meta‐analysis of transcriptional subtypes
title_sort immunophenotypes of pancreatic ductal adenocarcinoma: meta‐analysis of transcriptional subtypes
topic Tumor Immunology and Microenvironment
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767191/
https://www.ncbi.nlm.nih.gov/pubmed/30720864
http://dx.doi.org/10.1002/ijc.32186
work_keys_str_mv AT desantiagoines immunophenotypesofpancreaticductaladenocarcinomametaanalysisoftranscriptionalsubtypes
AT yauchristopher immunophenotypesofpancreaticductaladenocarcinomametaanalysisoftranscriptionalsubtypes
AT heijlara immunophenotypesofpancreaticductaladenocarcinomametaanalysisoftranscriptionalsubtypes
AT middletonmarkr immunophenotypesofpancreaticductaladenocarcinomametaanalysisoftranscriptionalsubtypes
AT markowetzflorian immunophenotypesofpancreaticductaladenocarcinomametaanalysisoftranscriptionalsubtypes
AT grabschheikei immunophenotypesofpancreaticductaladenocarcinomametaanalysisoftranscriptionalsubtypes
AT dustinmichaell immunophenotypesofpancreaticductaladenocarcinomametaanalysisoftranscriptionalsubtypes
AT sivakumarshivan immunophenotypesofpancreaticductaladenocarcinomametaanalysisoftranscriptionalsubtypes