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RETRACTED ARTICLE: Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-γ-induced immunologic dormancy of tumor-repopulating cells

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Liu, Yuying, Liang, Xiaoyu, Yin, Xiaonan, Lv, Jiadi, Tang, Ke, Ma, Jingwei, Ji, Tiantian, Zhang, Huafeng, Dong, Wenqian, Jin, Xun, Chen, Degao, Li, Yanchun, Zhang, Songyan, Xie, Heidi Q., Zhao, Bin, Zhao, Tong, Lu, Jinzhi, Hu, Zhuo-Wei, Cao, Xuetao, Qin, F. Xiao-Feng, Huang, Bo·2017·Nature Communications
DOI 10.1038/ncomms15207
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Abstract

Interactions with the immune system may lead tumorigenic cells into dormancy. However, the underlying molecular mechanism is poorly understood. Using a 3D fibrin gel model, we show that IFN-γ induces tumour-repopulating cells (TRCs) to enter dormancy through an indolamine 2,3-dioxygenase 1 (IDO1)-kynurenine (Kyn)-aryl hydrocarbon receptor (AhR)-p27 dependent pathway. Mechanistically, IFN-γ signalling triggers differentiated tumour cell apoptosis via STAT1; however, when IDO1 and AhR are highly expressed as in TRCs, IFN-γ results in IDO1/AhR-dependent p27 induction that prevents STAT1 signalling, thus suppressing the process of cell death and activating the dormancy program. Blocking the IDO/AhR metabolic circuitry not only abrogates IFN-γ-induced dormancy but also results in enhanced repression of tumour growth by IFN-γ-induced apoptosis of TRCs both in vitro and in vivo. These data present a previously unrecognized mechanism of inducing TRC dormancy by IFN-γ, suggesting a potential effective cancer immunotherapeutic modality through the combination of IFN-γ and IDO/AhR inhibitors.

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Research works printed but not linked: 53

  1. MacKie, R. M., Reid, R. & Junor, B. Fatal melanoma transferred in a donated kidney 16 years after melanoma surgery. N. Engl. J. Med. 348, 567–568 (2003). · DOI · Paper page
  2. Milton, C. A. et al. The transmission of donor-derived malignant melanoma to a renal allograft recipient. Clin. Transplant. 20, 547–550 (2006). · DOI
  3. Strauss, D. C. & Thomas, J. M. Transmission of donor melanoma by organ transplantation. Lancet Oncol. 11, 790–796 (2010). · DOI · Paper page
  4. Hamid, O. et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med. 369, 134–144 (2013). · DOI · Paper page
  5. Senzer, N. N. et al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J. Clin. Oncol. 27, 5763–5771 (2009). · DOI · Paper page
  6. Davila, M. L. et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci. Transl. Med. 6, 224–236 (2014). · DOI · Paper page
  7. Schreiber, R. D., Old, L. J. & Smyth, M. J. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331, 1565–1570 (2011). · DOI · Paper page
  8. Dunn, G. P., Old, L. J. & Schreiber, R. D. The three Es of cancer immunoediting. Annu. Rev. Immunol. 22, 329–360 (2004). · DOI · Paper page
  9. Sosa, M. S., Bragado, P. & Aguirre-Ghiso, J. A. Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat. Rev. Cancer 14, 611–622 (2014). · DOI · Paper page
  10. DuPage, M., Mazumdar, C., Schmidt, L. M., Cheung, A. F. & Jacks, T. Expression of tumour-specific antigens underlies cancer immunoediting. Nature 482, 405–409 (2012). · DOI · Paper page
  11. Matsushita, H. et al. Cancer exome analysis reveals a T cell dependent mechanism of cancer immunoediting. Nature 482, 400–404 (2012). · DOI · Paper page
  12. Koebel, C. M. et al. Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450, 903–907 (2007). · DOI · Paper page
  13. Li, Y. et al. Upregulation of cytosolic phosphoenolpyruvate carboxykinase is a critical metabolic event in melanoma cells that repopulate tumors. Cancer Res. 75, 1191–1196 (2015). · DOI
  14. Liu, J. et al. Soft fibrin gels promote selection and growth of tumorigenic cells. Nat. Mater. 11, 734–741 (2012). · DOI · Paper page
  15. Tan, Y. et al. Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression. Nat. Commun. 5, 4619 (2014). · DOI · Paper page
  16. Ma, J. et al. Reversing drug resistance of soft tumor-repopulating cells by tumor cell-derived chemotherapeutic microparticles. Cell Res. 26, 713–727 (2016). · DOI · Paper page
  17. Kusumbe, A. P. & Bapat, S. A. Cancer stem cells and aneuploid populations within developing tumors are the major determinants of tumor dormancy. Cancer Res. 69, 9245–9253 (2009). · DOI · Paper page
  18. Kobayashi, A. et al. Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone. J. Exp. Med. 208, 2641–2655 (2011). · DOI · Paper page
  19. Kleffel, S. & Schatton, T. Tumor dormancy and cancer stem cells: two sides of the same coin? Adv. Exp. Med. Biol. 734, 145–179 (2013). · DOI
  20. Noh, K. H. et al. Nanog signaling in cancer promotes stem-like phenotype and immune evasion. J. Clin. Invest. 122, 4077–4093 (2012). · DOI · Paper page
  21. Bruttel, V. S. & Wischhusen, J. Cancer stem cell immunology: key to understanding tumorigenesis and tumor immune escape? Front. Immunol. 5, 360 (2014). · DOI · Paper page
  22. Platanias, L. C. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat. Rev. Immunol. 5, 375–386 (2005). · DOI · Paper page
  23. Strehl, B. et al. Interferon-γ, the functional plasticity of the ubiquitin–proteasome system, and MHC class I antigen processing. Immunol. Rev. 207, 19–30 (2005). · DOI · Paper page
  24. Zhao, X. et al. Vaccines targeting tumor blood vessel antigens promote CD8(+) T cell-dependent tumor eradication or dormancy in HLA-A2 transgenic mice. J. Immunol. 188, 1782–1788 (2012). · doi:10.4049/jimmunol.1101644
  25. Shankaran, V. et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410, 1107–1111 (2001). · DOI · Paper page
  26. Zimmerer, R. M. et al. Functional features of cancer stem cells in melanoma cell lines. Cancer Cell Int. 13, 78–78 (2013). · DOI
  27. Monzani, E. et al. Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. Eur. J. Cancer 43, 935–946 (2007). · DOI · Paper page
  28. Takikawa, O., Habara-Ohkubo, A. & Yoshida, R. IFN-gamma is the inducer of indoleamine 2,3-dioxygenase in allografted tumor cells undergoing rejection. J. Immunol. 145, 1246–1250 (1990). · DOI
  29. Guillonneau, C. et al. CD40Ig treatment results in allograft acceptance mediated by CD8(+)CD45RC(low) T cells, IFN-γ, and indoleamine 2,3-dioxygenase. J. Clin. Invest. 117, 1096–1106 (2007). · DOI · Paper page
  30. DiNatale, B. C. et al. Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling. Toxicol. Sci. 115, 89–97 (2010). · DOI · Paper page
  31. Schroeder, J. C. et al. The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptor. Biochemistry 49, 393–400 (2010). · DOI · Paper page
  32. Chaveroux, C. et al. Regulating the expression of therapeutic transgenes by controlled intake of dietary essential amino acids. Nat. Biotech. 34, 746–751 (2016). · DOI
  33. Huang, B. et al. Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res. 66, 1123–1131 (2006). · DOI · Paper page
  34. Yeager, R. L., Reisman, S. A., Aleksunes, L. M. & Klaassen, C. D. Introducing the ‘TCDD-inducible AhR-Nrf2 gene battery’. Toxicol. Sci. 111, 238–246 (2009). · DOI · Paper page
  35. Nukaya, M., Moran, S. & Bradfield, C. A. The role of the dioxin-responsive element cluster between the Cyp1a1 and Cyp1a2 loci in aryl hydrocarbon receptor biology. Proc. Natl Acad. Sci. USA 106, 4923–4928 (2009). · DOI · Paper page
  36. Ning, Y. et al. IFNγ restores breast cancer sensitivity to fulvestrant by regulating STAT1, IFN regulatory factor 1, NF-κB, BCL2 family members, and signaling to caspase-dependent apoptosis. Mol. Cancer Ther. 9, 1274–1285 (2010). · DOI
  37. Sironi, J. J. & Ouchi, T. STAT1-induced apoptosis is mediated by caspases 2, 3 and 7. J. Biol. Chem. 279, 4066–4074 (2004). · DOI
  38. Zhai, L. et al. Molecular pathways: targeting IDO1 and other tryptophan dioxygenases for cancer immunotherapy. Clin. Cancer Res. 21, 5427–5433 (2015). · DOI · Paper page
  39. Holmgaard, R. B. et al. Tumor-expressed IDO recruits and activates MDSCs in a Treg-dependent manner. Cell Rep. 13, 412–424 (2015). · DOI · Paper page
  40. Godin-Ethier, J., Hanafi, L.-A., Piccirillo, C. A. & Lapointe, R. Indoleamine 2,3-dioxygenase expression in human cancers: clinical and immunologic perspectives. Clin. Cancer Res. 17, 6985–6991 (2011). · DOI · Paper page
  41. Ikeda, H., Old, L. J. & Schreiber, R. D. The roles of IFNγ in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev. 13, 95–109 (2002). · DOI · Paper page
  42. Street, S. E., Trapani, J. A., MacGregor, D. & Smyth, M. J. Suppression of lymphoma and epithelial malignancies effected by interferon gamma. J. Exp. Med. 196, 129–134 (2002). · DOI · Paper page
  43. Akira, S., Uematsu, S. & Takeuchi, O. Pathogen recognition and innate immunity. Cell 124, 783–801 (2006). · DOI · Paper page
  44. Ball, H. J. et al. Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice. Gene 396, 203–213 (2007). · DOI · Paper page
  45. Cui, T. X. et al. Myeloid derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2. Immunity 39, 611–621 (2013). · DOI · Paper page
  46. Kryczek, I. et al. IL-22(+)CD4(+) T cells promote colorectal cancer stemness via STAT3 transcription factor activation and induction of the methyltransferase DOT1L. Immunity 40, 772–784 (2014). · DOI · Paper page
  47. Lawson, D. A. et al. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells. Nature 526, 131–135 (2015). · DOI · Paper page
  48. Li, Q., Harden, J. L., Anderson, C. D. & Egilmez, N. K. Tolerogenic phenotype of IFN-γ-induced IDO+ dendritic cells is maintained via an autocrine IDO–kynurenine/AhR–IDO loop. J. Immunol. 197, 962–970 (2016). · DOI
  49. Sun, X. et al. IDO-competent-DCs induced by IFN-γ attenuate acute rejection in rat liver transplantation. J. Clin. Immunol. 32, 837–847 (2012). · DOI
  50. Dorand, R. D. et al. Cdk5 disruption attenuates tumor PD-L1 expression and promotes antitumor immunity. Science 353, 399–403 (2016). · DOI · Paper page
  51. Lipson, E. J. et al. Durable cancer regression off-treatment and effective re-induction therapy with an anti-PD-1 antibody. Clin. cancer Res. 19, 462–468 (2013). · DOI · Paper page
  52. Zou, W., Wolchok, J. D. & Chen, L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers and combinations. Sci. Transl. Med. 8, 328rv324–328rv324 (2016). · DOI · Paper page
  53. Hasegawa, H. et al. Dihydroflavonol BB-1, an extract of natural plant Blumea balsamifera, abrogates TRAIL resistance in leukemia cells. Blood 107, 679–688 (2006). · DOI

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Metadata

Authors
Liu, Y., Liang, X., Yin, X., Lv, J., Tang, K., Ma, J., Ji, T., Zhang, H., Dong, W., Jin, X., Chen, D., Li, Y., Zhang, S., Xie, H. Q., Zhao, B., Zhao, T., Lu, J., Hu, Z.-W., Cao, X., Qin, F. X.-F., & Huang, B.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-05-10
Volume
8
Issue
1
Pages
15207-15207
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms15207
OpenAlex
W2612537840
Cited by
212
References
14
FWCI
6.46
Type
journal article
Language
en
Status
Retracted
Update notices
retraction (2025-10-07)
Open access
gold
Licence

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CoChat. (2026). Citation check: RETRACTED ARTICLE: Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-γ-induced immunologic dormancy of tumor-repopulating cells. https://app.cochat.ai/papers/10.1038/ncomms15207
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Liu, Y., Liang, X., Yin, X., Lv, J., Tang, K., Ma, J., Ji, T., Zhang, H., Dong, W., Jin, X., Chen, D., Li, Y., Zhang, S., Xie, H. Q., Zhao, B., Zhao, T., Lu, J., Hu, Z.-W., Cao, X., . . . Huang, B. (2017). RETRACTED ARTICLE: Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-γ-induced immunologic dormancy of tumor-repopulating cells. Nature Communications. https://doi.org/10.1038/ncomms15207

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