Journal article
IDO1 Signaling through GCN2 in a Subpopulation of Gr-1 + Cells Shifts the IFNγ/IL6 Balance to Promote Neovascularization
Cancer immunology research, v 9(5), pp 514-528
May 2021
PMID: 33622713
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In addition to immunosuppression, it is generally accepted that myeloid-derived suppressor cells (MDSC) also support tumor angiogenesis. The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO1) has been implicated in promoting neovascularization through its positioning as a key regulatory node between the inflammatory cytokines IFNγ and IL6. Here, we report that within the heterogeneous expanse of Gr-1 MDSCs, both IDO1 expression and the ability to elicit neovascularization were associated with a minor subset of autofluorescent, CD11b cells. IDO1 expression was further restricted to a discrete, CD11c and asialo-GM1 double-positive subpopulation of these cells, designated here as IDVCs (IDO1-dependent vascularizing cells), due to the dominant role that IDO1 activity in these cells was found to play in promoting neovascularization. Mechanistically, the induction of IDO1 in IDVCs provided a negative-feedback constraint on the antiangiogenic effect of host IFNγ by intrinsically signaling for the production of IL6 through general control nonderepressible 2 (GCN2)-mediated activation of the integrated stress response. These findings reveal fundamental molecular and cellular insights into how IDO1 interfaces with the inflammatory milieu to promote neovascularization.
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Details
- Title
- IDO1 Signaling through GCN2 in a Subpopulation of Gr-1 + Cells Shifts the IFNγ/IL6 Balance to Promote Neovascularization
- Creators
- Souvik Dey - Lankenau Institute for Medical ResearchArpita Mondal - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PennsylvaniaJames B DuHadaway - Lankenau Institute for Medical Research, Wynnewood, PennsylvaniaErika Sutanto-Ward - Lankenau Institute for Medical Research, Wynnewood, PennsylvaniaLisa D Laury-Kleintop - Lankenau Institute for Medical Research, Wynnewood, PennsylvaniaSunil Thomas - Lankenau Institute for Medical ResearchGeorge C Prendergast - Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaLaura Mandik-Nayak - Lankenau Institute for Medical ResearchAlexander J Muller - Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
- Publication Details
- Cancer immunology research, v 9(5), pp 514-528
- Number of pages
- 15
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000647314900005
- Scopus ID
- 2-s2.0-85105268462
- Other Identifier
- 991021860661504721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Immunology
- Oncology