Blocking IDO activity to enhance anti-tumor immunity

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Tumors express potentially immunogenic antigens, yet the immune response to these antigens is typically profoundly suppressed. Patients with established tumors behave as if they were functionally tolerant to any antigens associated with the tumor. This tolerance reflects a process of active immune suppression elicited by the tumor, and represents a critical barrier to successful antitumor immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is a natural immunoregulatory mechanism contributes to immune suppression and tolerance in a variety of settings. In tumor-bearing hosts, animal models suggest that tumor-induced IDO helps create a tolerogenic milieu within the tumor and the associated tumor-draining lymph nodes. IDO directly suppresses the proliferation and differentiation of effector T cells, and markedly enhances the suppressor activity of regulatory T cells (Tregs). Together, these effects contribute to the inability of the immune system to respond effectively to tumor antigens. Treatment of tumor-bearing animals with IDO-inhibitor drugs enhances anti-tumor immune responses, and IDOinhibitors are synergistic with a variety of chemotherapeutic drugs, anti-tumor vaccines and other immunotherapy. Strategies to pharmacologically inhibit IDO may thus enhance immune-mediated responses following conventional chemotherapy, and may be synergistic with other forms of immunotherapy.

Original languageEnglish (US)
Pages (from-to)734-745
Number of pages12
JournalFrontiers in Bioscience - Elite
Volume4 E
Issue number2
StatePublished - Jan 1 2012

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Tumors
Immunity
Neoplasms
Bearings (structural)
Immunotherapy
T-cells
Antigens
Animals
Immune Tolerance
Cancer Vaccines
Chemotherapy
Immune system
Histocompatibility Antigens Class II
Neoplasm Antigens
Regulatory T-Lymphocytes
Pharmaceutical Preparations
Immune System
Animal Models
Lymph Nodes

Keywords

  • Adjuvant
  • Checkpoint Blockade
  • IDO
  • Immunotherapy
  • Indoleamine 2 3-Dioxygenase
  • Inhibitor
  • Review
  • Tolerance
  • Tumors
  • Vaccine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

Cite this

Blocking IDO activity to enhance anti-tumor immunity. / Munn, David H.

In: Frontiers in Bioscience - Elite, Vol. 4 E, No. 2, 01.01.2012, p. 734-745.

Research output: Contribution to journalArticle

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