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Chemo-Immunotherapy: Role of Indoleamine 2,3-Dioxygenase in Defining Immunogenic Versus Tolerogenic Cell Death in the Tumor Microenvironment

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Tumor Immune Microenvironment in Cancer Progression and Cancer Therapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1036))

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.

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Authors and Affiliations

  1. Department of Pediatrics, Augusta University (AU), Medical College of Georgia, Augusta, GA, USA

    Theodore S. Johnson & David H. Munn

  2. Georgia Cancer Center, Augusta, GA, USA

    Theodore S. Johnson, Tracy Mcgaha & David H. Munn

  3. Department of Immunology, University of Toronto, Toronto, ON, Canada

    Tracy Mcgaha

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  1. Theodore S. Johnson
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  2. Tracy Mcgaha
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  3. David H. Munn
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Correspondence to David H. Munn .

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  1. Department of Medicine and Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York, USA

    Pawel Kalinski

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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: Kalinski, P. (eds) Tumor Immune Microenvironment in Cancer Progression and Cancer Therapy. Advances in Experimental Medicine and Biology, vol 1036. Springer, Cham. https://doi.org/10.1007/978-3-319-67577-0_7

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