Indoleamine 2,3-dioxygenase and tumor-induced immune suppression

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Tumors express antigens to which the immune system should, in principle, be able to respond. Yet the immune response to tumors is usually weak or absent, and is seldom curative even with the best available immunotherapy. Functionally, patients with tumors behave as if they were tolerant to their tumor antigens. This state of acquired functional tolerance must be overcome in order for immunotherapy of cancer to succeed. Expression of indoleamine 2,3-dioxygenase (IDO) is a molecular mechanism that contributes to acquired peripheral tolerance in the immune system, and has been implicated in tumor-induced tolerance. Animal models suggest that IDO helps create an immunosuppressive and tolerance-inducing milieu within the tumor and the associated tumor-draining lymph nodes. IDO directly suppresses responses by effector T cells, and also creates potent bystander suppression by enhancing the inhibitory activity of local regulatory T cells (Tregs). In preclinical models, IDO-inhibitor drugs are synergistic with a number of chemotherapeutic agents, and enhance the efficacy of anti-tumor vaccines. Further, because IDO is induced in a variety of inflammatory settings, IDO may inadvertently act as an undesirable counter-regulatory antagonist that limits the efficacy of beneficial immune activators, such as vaccine adjuvants. Strategies to block IDO may thus be synergistic with chemotherapy, and may enhance the effectiveness of other forms of anti-tumor immunotherapy. Orally-bioavailable small-molecule inhibitors of the IDO pathway, such as 1-methyl-d-tryptophan, are now entering clinical trials.

Original languageEnglish (US)
Title of host publicationInnate Immune Regulation and Cancer Immunotherapy
PublisherSpringer New York
Pages303-318
Number of pages16
ISBN (Electronic)9781441999146
ISBN (Print)9781441999139
DOIs
StatePublished - Jan 1 2012

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Neoplasms
Immunotherapy
Neoplasm Antigens
Immune System
Bystander Effect
Peripheral Tolerance
Cancer Vaccines
Regulatory T-Lymphocytes
Immunosuppressive Agents
Vaccines
Animal Models
Lymph Nodes
Clinical Trials
T-Lymphocytes
Drug Therapy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Munn, D. H. (2012). Indoleamine 2,3-dioxygenase and tumor-induced immune suppression. In Innate Immune Regulation and Cancer Immunotherapy (pp. 303-318). Springer New York. https://doi.org/10.1007/9781441999146_17

Indoleamine 2,3-dioxygenase and tumor-induced immune suppression. / Munn, David H.

Innate Immune Regulation and Cancer Immunotherapy. Springer New York, 2012. p. 303-318.

Research output: Chapter in Book/Report/Conference proceedingChapter

Munn, DH 2012, Indoleamine 2,3-dioxygenase and tumor-induced immune suppression. in Innate Immune Regulation and Cancer Immunotherapy. Springer New York, pp. 303-318. https://doi.org/10.1007/9781441999146_17
Munn DH. Indoleamine 2,3-dioxygenase and tumor-induced immune suppression. In Innate Immune Regulation and Cancer Immunotherapy. Springer New York. 2012. p. 303-318 https://doi.org/10.1007/9781441999146_17
Munn, David H. / Indoleamine 2,3-dioxygenase and tumor-induced immune suppression. Innate Immune Regulation and Cancer Immunotherapy. Springer New York, 2012. pp. 303-318
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