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Transcriptional and immunohistological assessment of immune infiltration in pancreatic cancer.
PLoS One
  • Brady Bernard, Earle A. Chiles Research Institute, Providence Cancer Institute, Providence Portland Medical Center, Portland, Oregon, United States of America.
  • Venkatesh Rajamanickam, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR
  • Christopher Dubay, Providence Cancer Center
  • Brian D. Piening, Molecular Genomics Laboratory, Providence Portland Medical Center, Portland, OR; Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Cancer Center, Portland, OR.
  • Emilio Alonso, Earle A. Chiles Research Institute, Providence Cancer Institute, Providence Portland Medical Center, Portland, Oregon, United States of America.
  • Zeljka Jutric, Earle A. Chiles Research Institute, Providence Cancer Institute, Providence Portland Medical Center, Portland, Oregon, United States of America.
  • Ephraim Tang, Earle A. Chiles Research Institute, Providence Cancer Institute, Providence Portland Medical Center, Portland, Oregon, United States of America.
  • Pippa Newell, Earle A. Chiles Research Institute, Providence Cancer Institute, Providence Portland Medical Center, Portland, Oregon, United States of America.
  • Paul D Hansen, Providence Portland Medical Center, Portland, OR.
  • Terry R Medler, Earle A. Chiles Research Institute, Providence Portland Medical Center
  • Andrew J Gunderson, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon
  • Kristina H Young, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, OR, United States of America
  • Carlo Bifulco, Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, Portland, OR
  • Joanna Pucilowska, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR
  • Marka R Crittenden, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, Portland
  • Michael J Gough, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, Portland
Document Type
Article
Publication Date
1-1-2020
Keywords
  • Adenocarcinoma,
  • Adult,
  • Aged,
  • Aged, 80 and over,
  • Female,
  • Gene Expression Profiling,
  • Gene Expression Regulation, Neoplastic,
  • Humans,
  • Lymphocytes, Tumor-Infiltrating,
  • Male,
  • Middle Aged,
  • Pancreatic Neoplasms,
  • Prospective Studies,
  • T-Lymphocytes,
  • Tumor Microenvironment
Disciplines
Abstract

Pancreatic adenocarcinoma is characterized by a complex tumor environment with a wide diversity of infiltrating stromal and immune cell types that impact the tumor response to conventional treatments. However, even in this poorly responsive tumor the extent of T cell infiltration as determined by quantitative immunohistology is a candidate prognostic factor for patient outcome. As such, even more comprehensive immunophenotyping of the tumor environment, such as immune cell type deconvolution via inference models based on gene expression profiling, holds significant promise. We hypothesized that RNA-Seq can provide a comprehensive alternative to quantitative immunohistology for immunophenotyping pancreatic cancer. We performed RNA-Seq on a prospective cohort of pancreatic tumor specimens and compared multiple approaches for gene expression-based immunophenotyping analysis compared to quantitative immunohistology. Our analyses demonstrated that while gene expression analyses provide additional information on the complexity of the tumor immune environment, they are limited in sensitivity by the low overall immune infiltrate in pancreatic cancer. As an alternative approach, we identified a set of genes that were enriched in highly T cell infiltrated pancreatic tumors, and demonstrate that these can identify patients with improved outcome in a reference population. These data demonstrate that the poor immune infiltrate in pancreatic cancer can present problems for analyses that use gene expression-based tools; however, there remains enormous potential in using these approaches to understand the relationships between diverse patterns of infiltrating cells and their impact on patient treatment outcomes.

Clinical Institute
Cancer
Department
Oncology
Department
Earle A. Chiles Research Institute
Citation Information
Brady Bernard, Venkatesh Rajamanickam, Christopher Dubay, Brian D. Piening, et al.. "Transcriptional and immunohistological assessment of immune infiltration in pancreatic cancer." PLoS One (2020)
Available at: http://works.bepress.com/brian-piening/67/