Cancer Immunology, Immunotherapy

, Volume 59, Issue 11, pp 1655–1663

Non-hematopoietic expression of IDO is integrally required for inflammatory tumor promotion

Authors

  • Alexander J. Muller
    • Lankenau Institute for Medical Research
    • Kimmel Cancer Center, Jefferson Medical CollegeThomas Jefferson University
  • James B. DuHadaway
    • Lankenau Institute for Medical Research
  • Mee Young Chang
    • Lankenau Institute for Medical Research
  • Arivudinambi Ramalingam
    • Lankenau Institute for Medical Research
  • Erika Sutanto-Ward
    • Lankenau Institute for Medical Research
  • Janette Boulden
    • Lankenau Institute for Medical Research
  • Alejandro P. Soler
    • Lankenau Institute for Medical Research
    • Richfield Laboratory of Dermatopathology
  • Laura Mandik-Nayak
    • Lankenau Institute for Medical Research
    • Department of Microbiology and Immunology, Jefferson Medical CollegeThomas Jefferson University
  • Susan K. Gilmour
    • Lankenau Institute for Medical Research
    • Kimmel Cancer Center, Jefferson Medical CollegeThomas Jefferson University
    • Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical CollegeThomas Jefferson University
    • Lankenau Institute for Medical Research
    • Kimmel Cancer Center, Jefferson Medical CollegeThomas Jefferson University
    • Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical CollegeThomas Jefferson University
Original Article

DOI: 10.1007/s00262-010-0891-4

Cite this article as:
Muller, A.J., DuHadaway, J.B., Chang, M.Y. et al. Cancer Immunol Immunother (2010) 59: 1655. doi:10.1007/s00262-010-0891-4

Abstract

Indoleamine 2,3-dioxygenase (IDO) is generally considered to be immunosuppressive but recent findings suggest this characterization oversimplifies its role in disease pathogenesis. Recently, we showed that IDO is essential for tumor outgrowth in the classical two-stage model of inflammatory skin carcinogenesis. Here, we report that IDO loss did not exacerbate classical inflammatory responses. Rather, IDO induction could be elicited by environmental signals and tumor promoters as an integral component of the inflammatory tissue microenvironment even in the absence of cancer. IDO loss had limited impact on tumor outgrowth in carcinogenesis models that lacked an explicit inflammatory tumor promoter. In the context of inflammatory carcinogenesis where IDO was critical to tumor development, the most important source of IDO was radiation-resistant non-hematopoietic cells, consistent with evidence that loss of the IDO regulatory tumor suppressor gene Bin1 in transformed skin cells facilitates IDO-mediated immune escape by a cell autonomous mechanism. Taken together, our results identify IDO as an integral component of ‘cancer-associated’ inflammation that tilts the immune system toward tumor support. More generally, they promote the concept that mediators of immune escape and cancer-associated inflammation may be genetically synonymous.

Keywords

Indoleamine 2,3-dioxygenaseImmunosuppressionCarcinogenesis

Supplementary material

262_2010_891_MOESM1_ESM.tif (5.8 mb)
Supplementary material (TIFF 5.81 MB)

Copyright information

© Springer-Verlag 2010