Effects of indoleamine 2, 3-dioxygenase (IDO) silencing on immunomodulatory function and cancer-promoting characteristic of adipose-derived mesenchymal stem cells (ASCs).
Adipose Tissue
/ drug effects
Adult
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Cells, Cultured
Female
Humans
Immunologic Factors
/ metabolism
Indoleamine-Pyrrole 2,3,-Dioxygenase
/ pharmacology
Interferon-gamma
/ metabolism
Lymphocytes
/ drug effects
Mesenchymal Stem Cells
/ drug effects
Middle Aged
Neoplasms
/ drug therapy
T-Lymphocytes, Regulatory
/ drug effects
Young Adult
Indoleamine 2, 3-dioxygenase
Tumor cell
adipose derived mesenchymal stem cell
immunosuppression
regulatory T cell
Journal
Cell biology international
ISSN: 1095-8355
Titre abrégé: Cell Biol Int
Pays: England
ID NLM: 9307129
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
revised:
25
08
2021
received:
24
03
2021
accepted:
05
09
2021
pubmed:
10
9
2021
medline:
3
3
2022
entrez:
9
9
2021
Statut:
ppublish
Résumé
Indoleamine 2, 3-dioxygenase (IDO) catabolizes tryptophan, mediates immunomodulatory functions, and is released by stromal cells such as mesenchymal stem cells. The aims of this study were to investigate the effects of IDO silencing on immunosuppressive function of adipose-derived mesenchymal stem cells (ASCs), T cells phenotype, and the proliferation/migration of tumor cells. ASCs isolated from adipose tissues of healthy women were transfected with IDO-siRNA. Galectin-3, transforming growth factor-β1, hepatocyte growth factor, and interleukin-10 as immunomodulators were measured in ASCs using qRT-PCR. T cells phenotype, interferon-γ, and interleukin-17 expression were evaluated in peripheral blood lymphocytes (PBLs) cocultured with IDO silenced-ASCs by flow cytometry and qRT-PCR, respectively. Scratch assay was applied to assess the proliferation/migration of MDA-MB-231 cell line. Galectin-3 was upregulated (p ˂ 0.05) while hepatocyte growth factor was downregulated (p ˂ 0.05) in IDO-silenced ASCs compared to control groups. Regulatory T cells were inhibited in PBLs cocultured with IDO-silenced ASCs; also T helper2 was decreased in PBLs cocultured with IDO-silenced ASCs relative to the scramble group. IDO-silenced ASCs caused interferon-γ overexpression but interleukin-17 downregulation in PBLs. The proliferation/migration of MDA-MB-231 was suppressed after exposing to condition media of IDO-silenced ASCs compared with condition media of untransfected (p < 0.01) and scramble-transfected ASCs (p < 0.05). The results exhibited the weakened capacity of IDO-silenced ASCs for suppressing the immune cells and promoting the tumor cells' proliferation/migration. IDO suppression may be utilized as a strategy for cancer treatment. Simultaneous blocking of immunomodulators along with IDO inhibitors may show more effects on boosting the efficiency of immune-based cancer therapies.
Substances chimiques
Immunologic Factors
0
Indoleamine-Pyrrole 2,3,-Dioxygenase
0
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2544-2556Subventions
Organisme : Shiraz Institute for Cancer Research
ID : ICR100-500 and ICR100-504
Organisme : Shiraz University of Medical Sciences
ID : 96-01-74-14117
Informations de copyright
© 2021 International Federation for Cell Biology.
Références
Alipour, R., Karimi, M. M., Hashemi-Beni, B., Adib, M., Sereshki, N., & Sadeghi, F. (2017). Indoleamine 2, 3-dioxygenase is dispensable for the immunomodulatory function of stem cells from human exfoliated deciduous teeth. Cell Journal (Yakhteh), 18, 597-608.
Angerami, M. T., Suarez, G. V., Vecchione, M. B., Laufer, N., Ameri, D., Ben, G., Perez, H., Sued, O., Salomón, H., & Quiroga, M. F. (2017). Expansion of CD25-negative forkhead box P3-positive T cells during HIV and Mycobacterium tuberculosis infection. Frontiers in immunology, 8, 528.
Antony, P. A., & Restifo, N. P. (2002). Do CD4+ CD25+ immunoregulatory T cells hinder tumor immunotherapy? Journal of immunotherapy (Hagerstown, Md.: 1997), 25, p. 202.
Baban, B., Chandler, P. R., Johnson, B. A., Huang, L., Li, M., Sharpe, M. L., & Munn, D. H. (2011). Physiologic control of IDO competence in splenic dendritic cells. The Journal of Immunology, 187, 2329-2335.
Bahador, A., Hadjati, J., Hassannejad, N., Ghazanfari, H, Maracy, M., Jafari, S., Nourizadeh, M., & Nejadeh, A. (2014). Frequencies of CD4+ T regulatory cells and their CD25high and FoxP3high subsets augment in peripheral blood of patients with acute and chronic brucellosis. Osong Public Health and Research Perspectives, 5, 161-168. https://doi.org/10.1016/j.phrp.2014.04.008
Bonanno, G., Mariotti, A., Procoli, A., Folgiero, V., Natale, D., De Rosa, L., & Gambella, M. (2012). Indoleamine 2, 3-dioxygenase 1 (IDO1) activity correlates with immune system abnormalities in multiple myeloma. Journal of Translational Medicine, 10, 247.
Cagliani, J., Grande, D., Molmenti, E. P., Miller, E. J., & Rilo, H. L. (2017). Immunomodulation by mesenchymal stromal cells and their clinical applications. Journal of Stem Cell and Regenerative Biology, 3.
Ceccarelli, S., Pontecorvi, P., Anastasiadou, E., Napoli, C., & Marchese, C. (2020). Immunomodulatory effect of adipose-derived stem cells: the cutting edge of clinical application. Frontiers in Cell and Developmental Biology, 8, 236.
Chinnadurai, R., Rajan, D., Ng, S., McCullough, K., Arafat, D., Waller, E. K., Anderson, L. J., Gibson, G., & Galipeau, J. (2017). Immune dysfunctionality of replicative senescent mesenchymal stromal cells is corrected by IFNγ priming. Blood Advances, 1, 628-643.
Deng, Y., Yi, S., Wang, G., Cheng, J., Zhang, Y., Chen, W., Tai, Y., Chen, S., Chen, G., Liu, W., Zhang, Q., & Yang, Y. (2014). Umbilical cord-derived mesenchymal stem cells instruct dendritic cells to acquire tolerogenic phenotypes through the IL-6-mediated upregulation of SOCS1. Stem Cells and Development, 23, 2080-2092.
Díaz-Alvarez, L., & Ortega, E. (2017). The many roles of galectin-3, a multifaceted molecule, in innate immune responses against pathogens. Mediators of Inflammation, 2017, 9247574.
Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., & Horwitz, E. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315-317.
Eleftheriadis, T., Pissas, G., Antoniadi, G., Liakopoulos, V., Tsogka, K., Sounidaki, M., & Stefanidis, I. (2016). Differential effects of the two amino acid sensing systems, the GCN2 kinase and the mTOR complex 1, on primary human alloreactive CD4+ T-cells. International Journal of Molecular Medicine, 37, 1412-1420. https://doi.org/10.3892/ijmm.2016.2547
Ghannam, S., Pène, J., Torcy-Moquet, G., Jorgensen, C., & Yssel, H. (2010). Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. The Journal of Immunology, 185, 302-312.
Grohmann, U., & Puccetti, P. (2015). The coevolution of IDO1 and AhR in the emergence of regulatory T-cells in mammals. Frontiers in immunology, 6, 58.
Harrell, C. R., Fellabaum, C., Jovicic, N., Djonov, V., Arsenijevic, N., & Volarevic, V. (2019). Molecular mechanisms responsible for therapeutic potential of mesenchymal stem cell-derived secretome. Cells, 8, 467. https://doi.org/10.3390/cells8050467
Harrison, S. A., Marri, S. R., Chalasani, N., Kohli, R., Aronstein, W., Thompson, G. A., Irish, W., Miles, M. V., Xanthakos, S. A., Lawitz, E., Noureddin, M., Schiano, T. D., Siddiqui, M., Sanyal, A., Neuschwander-Tetri, B. A., & Traber, P. G. (2016). Randomised clinical study: GR-MD-02, a galectin-3 inhibitor, vs. placebo in patients having non-alcoholic steatohepatitis with advanced fibrosis. Alimentary Pharmacology & Therapeutics, 44, 1183-1198.
Jiang, W., & Xu, J. (2020). Immune modulation by mesenchymal stem cells. Cell Proliferation, 53, e12712.
Kamdje, A. H. N., Kamga, P. T., Simo, R. T., Vecchio, L., Etet, P. F. S., Muller, J. M., & Amvene, J. M. (2017). Mesenchymal stromal cells' role in tumor microenvironment: Involvement of signaling pathways. Cancer Biology & Medicine, 14, 129.
Lanz, T. V., Williams, S. K., Stojic, A., Iwantscheff, S., Sonner, J. K., Grabitz, C., & Sahm, F. (2017). Tryptophan-2, 3-Dioxygenase (TDO) deficiency is associated with subclinical neuroprotection in a mouse model of multiple sclerosis. Scientific Reports, 7, 41271.
Liang, C., Jiang, E., Yao, J., Wang, M., Chen, S., Zhou, Z., & Han, M. (2018). Interferon-γ mediates the immunosuppression of bone marrow mesenchymal stem cells on T-lymphocytes in vitro. Hematology, 23, 44-49.
Liu, M., Wang, X., Wang, L., Ma, X., Gong, Z., Zhang, S., & Li, Y. (2018). Targeting the IDO1 pathway in cancer: from bench to bedside. Journal of Hematology & Oncology, 11, 100.
Luz-Crawford, P., Kurte, M., Bravo-Alegría, J., Contreras, R., Nova-Lamperti, E., Tejedor, G., & Djouad, F. (2013). Mesenchymal stem cells generate a CD4+ CD25+ Foxp3+ regulatory T cell population during the differentiation process of Th1 and Th17 cells. Stem Cell Research & Therapy, 4, 65.
Melief, S. M., Visser, M., van der Burg, S. H., & Verdegaal, E. M. E. (2017). IDO and galectin-3 hamper the ex vivo generation of clinical grade tumor-specific T cells for adoptive cell therapy in metastatic melanoma. Cancer Immunology, Immunotherapy: CII, 66, 913-926.
Metghalchi, S., Vandestienne, M., Haddad, Y., Esposito, B., Dairou, J., Tedgui, A., Mallat, Z., Potteaux, S., & Taleb, S. (2018). Indoleamine 2 3-dioxygenase knockout limits angiotensin II-induced aneurysm in low density lipoprotein receptor-deficient mice fed with high fat diet. PLoS One, 13, e0193737.
Munn, D. H., & Mellor, A. L. (2016). IDO in the tumor microenvironment: Inflammation, counter-regulation, and tolerance. Trends in Immunology, 37, 193-207.
Le Naour, J., Galluzzi, L., Zitvogel, L., Kroemer, G., & Vacchelli, E. (2020). Trial watch: IDO inhibitors in cancer therapy. Oncoimmunology, 9, 1777625.
Nishikawa, H., & Sakaguchi, S. (2014). Regulatory T cells in cancer immunotherapy. Current Opinion in Immunology, 27, 1-7.
Orabona, C., & Grohmann, U. (2011). Indoleamine 2, 3-dioxygenase and regulatory function: Tryptophan starvation and beyond. Suppression and Regulation of Immune Responses (pp. Methods in Molecular Biology, 677, 269-280). https://doi.org/10.1007/978-1-60761-869-0_19
Owusu, B. Y., Galemmo, R., Janetka, J., & Klampfer, L. (2017). Hepatocyte growth factor, a key tumor-promoting factor in the tumor microenvironment. Cancers, 9, 35.
Patel, S. A., Meyer, J. R., Greco, S. J., Corcoran, K. E., Bryan, M., & Rameshwar, P. (2010). Mesenchymal stem cells protect breast cancer cells through regulatory T cells: Role of mesenchymal stem cell-derived TGF-beta. Journal of Immunology, 184, 5885-5894.
Pollizzi, K. N., & Powell, J. D. (2015). Regulation of T cells by mTOR: The known knowns and the known unknowns. Trends in Immunology, 36, 13-20.
Razmkhah, M., Abedi, N., Hosseini, A., Imani, M. T., Talei, A. R., & Ghaderi, A. (2015). Induction of T regulatory subsets from naïve CD4+ T cells after exposure to breast cancer adipose derived stem cells. Iranian Journal of Immunology, 12, 1-15.
Razmkhah, M., Jaberipour, M., Erfani, N., Habibagahi, M., Talei, A. R., & Ghaderi, A. (2011). Adipose derived stem cells (ASCs) isolated from breast cancer tissue express IL-4, IL-10 and TGF-β1 and upregulate expression of regulatory molecules on T cells: Do they protect breast cancer cells from the immune response? Cellular Immunology, 266, 116-122.
Razmkhah, M., Mansourabadi, Z., Mohtasebi, M. S., Talei, A. R., & Ghaderi, A. (2018). Cancer and normal adipose-derived mesenchymal stem cells (ASCs): Do they have differential effects on tumor and immune cells? Cell Biology International, 42, 334-343.
Rivera-Cruz, C. M., Shearer, J. J., Figueiredo Neto, M., & Figueiredo, M. L. (2017). The immunomodulatory effects of mesenchymal stem cell polarization within the tumor microenvironment niche. Stem Cells International, 2017, 2017. https://doi.org/10.1155/2017/4015039
Sakaguchi, S. (2004). Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annual Review of Immunology, 22, 531-562. https://doi.org/10.1146/annurev.immunol.21.120601.141122
Sioud, M., Mobergslien, A., Boudabous, A., & Fløisand, Y. (2010). Evidence for the involvement of galectin-3 in mesenchymal stem cell suppression of allogeneic T-cell proliferation. Scandinavian Journal of Immunology, 71, 267-274.
Sioud, M., Nyakas, M., Saebøe-Larssen, S., Mobergslien, A., Aamdal, S., & Kvalheim, G. (2016). Diversification of antitumour immunity in a patient with metastatic melanoma treated with ipilimumab and an IDO-silenced dendritic cell vaccine. Case Reports in Medicine, 2016, 2016-2017.
Souza, B. S. dF., Silva, K. N. d, Silva, D. N., Rocha, V. P. C., Paredes, B. D., Azevedo, C. M., & Santos, R. R. d., (2017). Galectin-3 knockdown impairs survival, migration, and immunomodulatory actions of mesenchymal stromal cells in a mouse model of Chagas disease cardiomyopathy.
Tang, D., Yue, L., Yao, R., Zhou, L., Yang, Y., Lu, L., & Gao, W. (2017). P53 prevent tumor invasion and metastasis by down-regulating IDO in lung cancer. Oncotarget, 8, 54548-54557.
Tsai, H.-F., Wu, C.-S., Chen, Y.-L., Liao, H.-J., Chyuan, I.-T., & Hsu, P.-N. (2016). Galectin-3 suppresses mucosal inflammation and reduces disease severity in experimental colitis. Journal of Molecular Medicine, 94, 545-556.
Tucker, H. A., & Bunnell, B. A. (2011). Characterization of human adipose-derived stem cells using flow cytometry. Adipose-Derived, Methods in Molecular Biology (pp. 702, 121-131). https://doi.org/10.1007/978-1-61737-960-4_10
Vigneron, N., van Baren, N., & Van den Eynde, B. J. (2015). Expression profile of the human IDO1 protein, a cancer drug target involved in tumoral immune resistance. Oncoimmunology, 4:e1003012.
Volarevic, V., Zdravkovic, N., Harrell, C. R., Arsenijevic, N., & Fellabaum, C. (2019). Galectin-3 regulates indoleamine-2,3-dioxygenase-dependent cross-talk between colon-infiltrating dendritic cells and T regulatory cells and may represent a valuable biomarker for monitoring the progression of ulcerative colitis. Cells, 8, 709. https://doi.org/10.3390/cells8070709
Wang, Y., Chen, X., Cao, W., & Shi, Y. (2014). Plasticity of mesenchymal stem. Cells in immunomodulation: pathological and therapeutic implications. Nature Immunology, 15, 1009-1016. https://doi.org/10.1038/ni.3002
Yen, M., Weng, T., Chen, Y., Lin, C., Chen, C., Wang, C., & Lai, M.-D. (2013). An HDAC inhibitor enhances cancer therapeutic efficiency of RNA polymerase III promoter-driven IDO shRNA. Cancer Gene Therapy, 20, 351-357.
Zhang, W., Zhang, J., Zhang, Z., Guo, Y., Wu, Y., Wang, R., Wang, L., Mao, S., & Yao, X. (2019). Overexpression of indoleamine 2,3-dioxygenase 1 promotes epithelial-mesenchymal transition by activation of the IL-6/STAT3/PD-L1 pathway in bladder cancer. Translational Oncology, 12, 485-492.
Zhou, Y., Yamamoto, Y., Xiao, Z., & Ochiya, T. (2019). The immunomodulatory functions of mesenchymal stromal/stem cells mediated via paracrine activity. Journal of Clinical Medicine, 8, 1025.