IDO1 is an Integral Mediator of Inflammatory Neovascularization

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• 作者：Arpita Mondal^a ; ^b ; Courtney Smith^a ; ¹ ; James B. DuHadaway^a ; Erika Sutanto-Ward^a ; George C. Prendergast^a ; ^c ; Arturo Bravo-Nuevo^a ; ² ; Alexander J. Muller^a ; ^c ; ^{muller@limr.org}
• 关键词：Indoleamine 2 ; 3-dioxygenase ; Angiogenesis ; Lung metastasis ; Oxygen-induced retinopathy ; Interferon-gamma ; Interleukin 6 ; Inflammation ; Tryptophan
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：14
• 期：Complete
• 页码：74-82
• 全文大小：1562 K
• 卷排序：14

文摘

As a result of IDO1 loss, NV (neovascularization) is reduced in pulmonary metastasis and oxygen-induced retinopathy models IFNγ, an upstream inflammatory cytokine, is required for the reduced NV and pulmonary metastasis outgrowth due to IDO1 loss Loss of IL6, a downstream inflammatory cytokine, has similar IFNg-dependent effects on NV and metastasis as loss of IDO1The tryptophan-catabolizing enzyme IDO1 has garnered clinical attention as a potential immuno-oncology target. In this report, Mondal, et al. demonstrate an additional role for IDO1 in supporting neovascularization – the development of new blood vessels that contributes to cancer and other diseases. IDO1's involvement in neovascularization is confirmed in a retinopathy model and correlated with tumor outgrowth in a pulmonary metastasis model. The impact of IDO1 loss on neovascularization is shown to be dependent on IFNγ and mimicked by the loss of IL6, two inflammatory cytokines that control and are controlled by IDO1 respectively, advancing the concept of IDO1 as an orchestrator of tumor-promoting inflammation.