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Isolation and Characterization of Patient-derived Pancreatic Ductal Adenocarcinoma Organoid Models
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Genotyping and expression analysis of IDO2 in human pancreatic cancer: a novel, active target

Agnieszka K Witkiewicz1, Christina L Costantino, Richard Metz

  • 1Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Journal of the American College of Surgeons
|May 30, 2009
PubMed
Abstract

Insights

Indoleamine 2,3-dioxygenase-2 (IDO2) is expressed in pancreatic cancer, even with genetic variations. This suggests IDO2 may be a therapeutic target for pancreatic ductal adenocarcinoma (PDA) treatment.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • The indoleamine 2,3-dioxygenase-2 (IDO2) gene has functional polymorphisms that can abolish its enzymatic activity.
  • IDO2 enzyme expression in primary pancreatic ductal adenocarcinomas (PDA) may enable cancer cells to evade immune detection.

Purpose of the Study:

  • To investigate the expression of the IDO2 enzyme in pancreatic ductal adenocarcinomas.
  • To determine if genetic polymorphisms in IDO2 affect its expression in PDA.
  • To assess the potential of IDO2 as a therapeutic target in PDA.

Main Methods:

  • Sequencing of the IDO2 gene in 36 pancreatic specimens.
  • Evaluation of IDO2 expression in PDA tissue and pancreatic cancer cell lines.
  • Analysis of IDO2 genetic polymorphisms (R248W and Y359STOP).

Main Results:

  • 75% of the resected patient cohort were estimated to have an active IDO2 enzyme, with 58% having at least one functional allele.
  • IDO2 was expressed in PDA tissue across all genetic polymorphic subgroups.
  • IDO2 protein expression was detected in pancreatic cancer cell lines after interferon-gamma exposure.

Conclusions:

  • This is the first study to report IDO2 expression in PDA, indicating that genetic polymorphisms do not prevent interferon-gamma-inducible protein expression.
  • The findings strongly suggest that the IDO inhibitor d-1-methyl-tryptophan may be a potential treatment for PDA.
  • IDO2 expression in PDA warrants further investigation as a therapeutic target.

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