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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Holmgaard RB,Zamarin D,Li Y,Gasmi B,Munn DH,Allison JP,Merghoub T,Wolchok JDdoi
10.1016/j.celrep.2015.08.077subject
Has Abstractpub_date
2015-10-13 00:00:00pages
412-24issue
2issn
2211-1247pii
S2211-1247(15)00990-0journal_volume
13pub_type
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