Interferon-Induced IDO1 Mediates Radiation Resistance and Is a Therapeutic Target in Colorectal Cancer

Cancer Immunology Research
Baosheng ChenMatthew A Ciorba

Abstract

Colorectal cancer is a major cause of mortality worldwide. Chemotherapy and radiation remain standard treatment for locally advanced disease, with current immune-targeting therapies applying to only a small subset of patients. Expression of the immuno-oncology target indoleamine 2,3 dioxygenase 1 (IDO1) is associated with poor colorectal cancer clinical outcomes but is understudied as a potential treatment target. In this study, we examined the interaction between the IDO1 pathway and radiotherapy in colorectal cancer. We used human and mouse colorectal cancer cell lines, organoids, mouse syngeneic colorectal cancer tumor graft models, and colorectal cancer tissues from patients who received radiotherapy. IDO1 activity was blocked using the clinical IDO1 inhibitor epacadostat and by genetic disruption. We found that radiation induced IDO1 overexpression in colorectal cancer through type I and II IFN signaling. IDO1 enzymatic activity directly influenced colorectal cancer radiation sensitivity. IDO1 inhibition sensitized colorectal cancer to radiation-induced cell death, whereas the IDO1 metabolite kynurenine promoted radioprotection. IDO1 inhibition also potentiated Th1 cytokines and myeloid cell-modulating factors in the tumor...Continue Reading

References

Jun 14, 2005·Nature Immunology·Gavin P DunnRobert D Schreiber
Nov 23, 2006·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Kathleen C F SheehanRobert D Schreiber
Feb 26, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthew A CiorbaWilliam F Stenson
Apr 28, 2010·Gastroenterology·C Richard Boland, Ajay Goel
Aug 9, 2011·Inflammatory Bowel Diseases·Nitin K GuptaMatthew A Ciorba
Oct 7, 2011·Nature·Christiane A OpitzMichael Platten
Mar 9, 2012·The New England Journal of Medicine·Michael A PostowJedd D Wolchok
Jan 25, 2013·Cancer Immunology, Immunotherapy : CII·Hatem SolimanStefan Ambs
Jan 3, 2014·The Journal of Clinical Investigation·Liufu DengYang-Xin Fu
Apr 2, 2014·Nature Reviews. Gastroenterology & Hepatology·Martin Hauer-JensenH Jervoise N Andreyev
Apr 9, 2014·Cancer Immunology, Immunotherapy : CII·George C PrendergastAlexander J Muller
Dec 31, 2014·Journal of Visualized Experiments : JoVE·Daniel E BauerStuart H Orkin
Apr 16, 2015·Cancer Treatment Reviews·Kobe ReyndersDirk De Ruysscher
Jun 2, 2015·The New England Journal of Medicine·Dung T LeLuis A Diaz
Aug 25, 2015·Translational Research : the Journal of Laboratory and Clinical Medicine·Srikanth SanthanamMatthew A Ciorba
Sep 29, 2015·Cell Reports·Rikke B HolmgaardJedd D Wolchok
Nov 1, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lijie ZhaiDerek A Wainwright
Mar 17, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Arta M MonjazebWilliam J Murphy
Nov 28, 2016·EBioMedicine·Arpita MondalAlexander J Muller
Dec 27, 2016·Science Immunology·Michael SpiottoRalph R Weichselbaum
Jan 6, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gregory L BeattyThomas F Gajewski
Aug 12, 2017·Frontiers in Immunology·Simone Di FrancoGiorgio Stassi
Nov 10, 2017·Cancer Research·Weili WangFeng-Ming Spring Kong
Jan 23, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael J OvermanThierry André
Feb 17, 2018·Nature Reviews. Cancer·Wilfred NgwaSilvia C Formenti
Mar 1, 2018·Frontiers in Immunology·Ping XueYufeng Zhou
Sep 12, 2018·Seminars in Immunopathology·Alexander J MullerGeorge C Prendergast
Sep 27, 2018·Frontiers in Oncology·Eric FoxGeorge C Prendergast
Dec 24, 2018·Seminars in Radiation Oncology·Joshua E LewisDavid A Boothman
Feb 15, 2019·Nature Reviews. Drug Discovery·Michael PlattenChristiane A Opitz

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Citations

Jun 9, 2020·The Journal of Nutrition·David M Alvarado, Matthew A Ciorba
Nov 27, 2020·International Journal of Molecular Sciences·Quinn Storozynsky, Mary M Hitt
Jan 19, 2021·Biochimie·Xiao-Han Liu, Xiao-Yue Zhai
Dec 12, 2020·Translational Research : the Journal of Laboratory and Clinical Medicine·Ebunoluwa E OtegbeyeMatthew A Ciorba
Apr 23, 2021·Journal of Hematology & Oncology·Kai TangBin Yu
May 2, 2021·Journal for Immunotherapy of Cancer·Juha P VäyrynenJonathan A Nowak
May 6, 2021·International Journal of Molecular Sciences·Yulia I NussbaumJonathan B Mitchem
Jun 5, 2021·Journal for Immunotherapy of Cancer·Shakoora A SabreeGeorge J Weiner
Jul 27, 2021·Frontiers in Oncology·Karl-Göran Tranberg
Aug 29, 2021·International Journal of Radiation Oncology, Biology, Physics·Steven H LinTheodore S Lawrence

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