Chemo-immunotherapy: Role of indoleamine 2,3-dioxygenase in defining immunogenic versus tolerogenic cell death in the tumor microenvironment

Research output: Chapter in Book/Report/Conference proceedingChapter

13 Scopus citations

Abstract

In certain settings, chemotherapy can trigger an immunogenic form of tumor cell death. More often, however, tumor cell death after chemotherapy is not immunogenic, and may be actively tolerizing. However, even in these settings the dying tumor cells may be much more immunogenic than previously recognized, if key suppressive immune checkpoints such as indoleamine 2,3-dioxygenase (IDO) can be blocked. This is an important question, because a robust immune response to dying tumor cells could potentially augment the efficacy of conventional chemotherapy, or enhance the strength and duration of response to other immunologic therapies. Recent findings using preclinical models of self-tolerance and autoimmunity suggest that IDO and related downstream pathways may play a fundamental role in the decision between tolerance versus immune activation in response to dying cells. Thus, in the period of tumor cell death following chemotherapy or immunotherapy, the presence of IDO may help dictate the choice between dominant immunosuppression versus inflammation, antigen cross-presentation, and epitope spreading. The IDO pathway thus differs from other checkpoint-blockade strategies, in that it affects early immune responses, at the level of inflammation, activation of antigen-presenting cells, and initial cross-presentation of tumor antigens. This “up-stream” position may make IDO a potent target for therapeutic inhibition.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages91-104
Number of pages14
DOIs
StatePublished - 2017

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1036
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Checkpoint
  • Chemotherapy
  • IDO
  • Immunotherapy
  • Indoleamine 2,3-dioxygenase
  • Radiation
  • Tolerance
  • Tumor
  • Tumor microenvironment

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Johnson, T. S., Mcgaha, T., & Munn, D. H. (2017). Chemo-immunotherapy: Role of indoleamine 2,3-dioxygenase in defining immunogenic versus tolerogenic cell death in the tumor microenvironment. In Advances in Experimental Medicine and Biology (pp. 91-104). (Advances in Experimental Medicine and Biology; Vol. 1036). Springer New York LLC. https://doi.org/10.1007/978-3-319-67577-0_7