Back to Search
Start Over
Tumor-Expressed IDO Recruits and Activates MDSCs in a Treg-Dependent Manner.
- Source :
-
Cell reports [Cell Rep] 2015 Oct 13; Vol. 13 (2), pp. 412-24. Date of Electronic Publication: 2015 Sep 24. - Publication Year :
- 2015
-
Abstract
- Indoleamine 2,3-dioxygenase (IDO) has been described as a major mechanism of immunosuppression in tumors, though the mechanisms of this are poorly understood. Here, we find that expression of IDO by tumor cells results in aggressive tumor growth and resistance to T-cell-targeting immunotherapies. We demonstrate that IDO orchestrates local and systemic immunosuppressive effects through recruitment and activation of myeloid-derived suppressor cells (MDSCs), through a mechanism dependent on regulatory T cells (Tregs). Supporting these findings, we find that IDO expression in human melanoma tumors is strongly associated with MDSC infiltration. Treatment with a selective IDO inhibitor in vivo reversed tumor-associated immunosuppression by decreasing numbers of tumor-infiltrating MDSCs and Tregs and abolishing their suppressive function. These findings establish an important link between IDO and multiple immunosuppressive mechanisms active in the tumor microenvironment, providing a strong rationale for therapeutic targeting of IDO as one of the central regulators of immune suppression.<br /> (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Movement
Cells, Cultured
Humans
Immunosuppressive Agents pharmacology
Indoleamine-Pyrrole 2,3,-Dioxygenase pharmacology
Mice
Myeloid Cells drug effects
Myeloid Cells physiology
Indoleamine-Pyrrole 2,3,-Dioxygenase immunology
Myeloid Cells immunology
Neoplasms immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 13
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 26411680
- Full Text :
- https://doi.org/10.1016/j.celrep.2015.08.077