IDO1 in cancer: a Gemini of immune checkpoints

Lijie Zhai, Erik Ladomersky, Alicia Lenzen, Brenda Nguyen, Ricky Patel, Kristen L. Lauing, Meijing Wu, Derek A. Wainwright*

*Corresponding author for this work

Research output: Contribution to journalReview article

40 Scopus citations

Abstract

Indoleamine 2, 3-dioxygenase 1 (IDO1) is a rate-limiting metabolic enzyme that converts the essential amino acid tryptophan (Trp) into downstream catabolites known as kynurenines. Coincidently, numerous studies have demonstrated that IDO1 is highly expressed in multiple types of human cancer. Preclinical studies have further introduced an interesting paradox: while single-agent treatment with IDO1 enzyme inhibitor has a negligible effect on decreasing the established cancer burden, approaches combining select therapies with IDO1 blockade tend to yield a synergistic benefit against tumor growth and/or animal subject survival. Given the high expression of IDO1 among multiple cancer types along with the lack of monotherapeutic efficacy, these data suggest that there is a more complex mechanism of action than previously appreciated. Similar to the dual faces of the astrological Gemini, we highlight the multiple roles of IDO1 and review its canonical association with IDO1-dependent tryptophan metabolism, as well as documented evidence confirming the dispensability of enzyme activity for its immunosuppressive effects. The gene transcript levels for IDO1 highlight its strong association with T-cell infiltration, but the lack of a universal prognostic significance among all cancer subtypes. Finally, ongoing clinical trials are discussed with consideration of IDO1-targeting strategies that enhance the efficacy of immunotherapy for cancer patients.

Original languageEnglish (US)
Pages (from-to)447-457
Number of pages11
JournalCellular and Molecular Immunology
Volume15
Issue number5
DOIs
StatePublished - May 1 2018

Keywords

  • IDO
  • Treg
  • glioblastoma
  • glioma
  • immunosuppression
  • immunotherapy
  • kynurenine
  • melanoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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  • Cite this

    Zhai, L., Ladomersky, E., Lenzen, A., Nguyen, B., Patel, R., Lauing, K. L., Wu, M., & Wainwright, D. A. (2018). IDO1 in cancer: a Gemini of immune checkpoints. Cellular and Molecular Immunology, 15(5), 447-457. https://doi.org/10.1038/cmi.2017.143