Journal of Molecular Medicine

, Volume 86, Issue 2, pp 145–160

IDO-expressing regulatory dendritic cells in cancer and chronic infection

Review

DOI: 10.1007/s00109-007-0262-6

Cite this article as:
Popov, A. & Schultze, J.L. J Mol Med (2008) 86: 145. doi:10.1007/s00109-007-0262-6

Abstract

Immune evasion and T cell tolerance induction have been associated both with malignant disease and chronic infection. In recent years, increasing evidence has been accumulated that antigen-presenting cells such as dendritic cells (DC) play a major role in immune regulation. They are not only involved in the induction of immunity but also can inhibit immune responses. Interesting parallels for major molecular mechanisms involved in turning DC from stimulatory to regulatory cells have been uncovered between malignant disease and chronic infection. Apparently, not only inhibitory cytokines such as IL-10 seem to play a role, but also metabolic mechanisms dysregulating tryptophan metabolism, thereby, leading to inhibition of T cells and pathogens. We focus here on recent findings establishing the tryptophan catabolizing enzyme indoleamine-pyrrole 2,3 dioxygenase (IDO) as a central feature of DC with regulatory function both in cancer and chronic infection. Induction of enzymatically active IDO can be triggered by various soluble and membrane-bound factors, and in general, require interferon (IFN) signaling. In addition, based on the most recently established link between tumor necrosis factor alpha (TNFα), prostaglandin E2 and IDO, a new model of regulation of IDO in context of cancer and infection is proposed. In light of the increasing use of anti-TNFα drugs, these findings are also of great interest to the clinician scientist.

Keywords

Dendritic cells Immune tolerance Tumor Infection Prostaglandin TNF 

Abbreviations

APC

antigen-presenting cells

BDCA

blood dendritic cell antigen

COX-2

cyclooxygenase-2

CTLs

cytotoxic T lymphocytes

DC

dendritic cells

DCreg

regulatory dendritic cells

EP2

prostaglandin E2 receptor 2

FoxP3

Forkhead box P3

GITR

glucocorticoid-induced tumor necrosis factor receptor

HIV

human immunodeficiency virus

HO-1

heme oxygenase-1

ICSBP1

interferon consensus sequence-binding protein 1

IDO

indoleamine-pyrrole 2,3 dioxygenase (INDO)

IFN

interferon

ILT

immunologlobulin-like transcripts

INOS

inducible nitric oxide synthase

IRF-1

interferon regulatory factor 1

ISRE

interferon-stimulated response elements

Mo-DC

monocyte-derived DC

MS

multiple sclerosis, pDC-plasmacytoid DC

PGE2

prostaglandin E2

RA

rheumatoid arthritis

SOCS3

suppressor of cytokine signaling 3

STAT

signal transducer and activator of transcription

TDLN

tumor-draining lymph nodes

TLR

toll-like receptor

Tregs

regulatory T cells

TYROBP

tyro protein tyrosine kinase-binding protein

VEGF

vascular endothelial growth factor.

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Molecular Tumor Biology and Tumor ImmunologyClinic I for Internal MedicineCologneGermany
  2. 2.Cologne Center for GenomicsUniversity of CologneCologneGermany
  3. 3.Molekulare Tumorbiologie und Tumorimmunologie, Klinik I für Innere MedizinUniversitätsklinikum KölnKölnGermany