Review Article

Overview of Interferon: Characteristics, signaling and anti-cancer effect

Kangjian Zhang*, Huaiyuan Wang and Haijun Hu

Published: 25 April, 2017 | Volume 1 - Issue 1 | Pages: 001-016

Interferons are multifunctional cytokines widely used in clinical settings as an anti-viral drug. In addition, interferon’s exhibit anti-cancer and anti-bacterial effects. Nearly two thousand papers related to interferon are published each year, which illustrates the importance placed by researchers on the study of interferon. This review focuses on recent advances in the study of interferon, particularly in the areas of its mechanism of anti-cancer effect and signal transduction. We also describe the tumor resistance to interferon and the side-effect of interferon-based therapy, which leads to an expectation of future research of interferon.

Read Full Article HTML DOI: 10.29328/journal.hjb.1001001 Cite this Article Read Full Article PDF


Interferon; Anti-cancer effect; Signal transduction; Side effecton



  1. Borden EC, Sen GC, Uze G, Silverman RH, Ransohoff RM, et al. Interferons at age 50: past, current and future impact on biomedicine. Nat Rev Drug Discov. 2007; 6: 975-990. Ref.: https://goo.gl/pNdXwZ
  2. Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, et al. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol. 2003; 4: 69-77. Ref.: https://goo.gl/CKhZVH
  3. Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, et al. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol. 2003; 4: 63-68. Ref.: https://goo.gl/QbVahF
  4. Prokunina-Olsson L, Muchmore B, Tang W, Pfeiffer RM, Park H, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genetics. 2013; 45: 164-171. Ref.: https://goo.gl/jf8xKD
  5. Weiss DL. Interferons and Interferon Inducers. JAMA. 1973; 226: 570. Ref.: https://goo.gl/KC9LyX
  6. Wheelock EF. Interferon-like virus-inhibitor induced in human leukocytes by hytohemagglutinin. Science. 1965; 149: 310-311. Ref.: https://goo.gl/YV22cd
  7. Freshman MM, Merigan TC, Remington JS, Brownlee IE. In vitro and in vivo antiviral action of an interferon-like substance induced by Toxoplasma gondii. Exp Biol Med. 1966; 123: 862-866. Ref.: https://goo.gl/M3Iunj
  8. Li Y, Stafford WF, Hesselberg M, Hayes D, Wu Z, et al. Characterization of the self-association of human interferon-alpha2b, albinterferon-alpha2b, and pegasys. J Pharm Sci. 2012; 101: 68-80. Ref.: https://goo.gl/xKkrPE
  9. Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, et al. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol. 2003; 4: 63-68. Ref.: https://goo.gl/HzznrC
  10. Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, et al. IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol. 2003; 4: 69-77. Ref.: https://goo.gl/F6Pnma
  11. Prokunina-Olsson L, Muchmore B, Tang W, Pfeiffer RM, Park H, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet. 2013. Ref.: https://goo.gl/CK0TQz
  12. Hamming OJ, Terczyńska‐Dyla E, Vieyres G, Dijkman R, Jørgensen SE, et al. Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses. EMBO J. 2013; 32: 3055-3065. Ref.: https://goo.gl/zjFOQy
  13. Van Boxel-Dezaire AH, Rani MR, Stark GR. Complex modulation of cell type-specific signaling in response to type I interferons. Immunity. 2006; 25: 361-372. Ref.: https://goo.gl/iqXiV0
  14. Shiba M, Nonomura N, Nakai Y, Nakayama M, Takayama H, et al. Type-I interferon receptor expression: its circadian rhythm and downregulation after interferon-alpha administration in peripheral blood cells from renal cancer patients. Int J Urol. 2009; 16: 356-359. Ref.: https://goo.gl/vIuXPS
  15. Baychelier F, Nardeux PC, Cajean-Feroldi C, Ermonval M, Guymarho J, et al. Involvement of the Gab2 scaffolding adapter in type I interferon signalling. Cell Signal. 2007; 19: 2080-2087. Ref.: https://goo.gl/XSTBT6
  16. De Weerd NA, Vivian JP, Nguyen TK, Mangan NE, Gould JA, et al. Structural basis of a unique interferon-[beta] signaling axis mediated via the receptor IFNAR1. Nat Immunol. 2013; 14: 901-907. Ref.: https://goo.gl/xjVkq4
  17. Kaur S, Platanias LC. IFN-[beta]-specific signaling via a unique IFNAR1 interaction. Nat Immunol. 2013; 14: 884-885. Ref.: https://goo.gl/A1MSx5
  18. Ahmed CM, Noon-Song EN, Kemppainen K, Pascalli MP, Johnson HM. Type I IFN receptor controls activated TYK2 in the nucleus: implications for EAE therapy. J Neuroimmunol. 2013; 254: 101-109. Ref.: https://goo.gl/JwQhlC
  19. Larkin Iii J, Johnson HM, Subramaniam PS. Differential nuclear localization of the IFNGR-1 and IFNGR-2 subunits of the IFN-γ receptor complex following activation by IFN-γ. J Interferon Cytokine Res. 2000; 20: 565-576. Ref.: https://goo.gl/z5reog
  20. Subramaniam PS, Johnson HM. Lipid microdomains are required sites for the selective endocytosis and nuclear translocation of IFN-γ, its receptor chain IFN-γ receptor-1, and the phosphorylation and nuclear translocation of STAT1α. J Immunol. 2002; 169: 1959-1969. Ref.: https://goo.gl/203W8b
  21. Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, et al. Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature. 2007; 449: 919-922. Ref.: https://goo.gl/23YTwH
  22. Ji J, Shi J, Budhu A, Yu Z, Forgues M, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 2009; 361: 1437-1447. Ref.: https://goo.gl/tUY2tw
  23. Siegrist F, Singer T, Certa U. MicroRNA Expression Profiling by Bead Array Technology in Human Tumor Cell Lines Treated with Interferon-Alpha-2a. Biol Proced Online. 2009; 11: 113-129. Ref.: https://goo.gl/JGliZC
  24. Sekiya Y, Ogawa T, Iizuka M, Yoshizato K, Ikeda K, et al. Down-regulation of cyclin E1 expression by microRNA-195 accounts for interferon-beta-induced inhibition of hepatic stellate cell proliferation. J Cell Physiol. 2011; 226: 2535-2542. Ref.: https://goo.gl/BzcjxN
  25. Critchley-Thorne RJ, Simons DL, Yan N, Miyahira AK, Dirbas FM, et al. Impaired interferon signaling is a common immune defect in human cancer. Proc Natl Acad Sci U S A. 2009; 106: 9010-9015. Ref.: https://goo.gl/LbEUaU
  26. Alexander WS, Starr R, Fenner JE, Scott CL, Handman E, et al. SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell. 1999; 98: 597-608. Ref.: https://goo.gl/XNPTFU
  27. Yoshimura A, Naka T, Kubo M. SOCS proteins, cytokine signalling and immune regulation. Nat Rev Immunol. 2007; 7: 454-465. Ref.: https://goo.gl/KZ22lo
  28. Zimmerer JM, Lesinski GB, Kondadasula SV, Karpa VI, Lehman A, et al. IFN-alpha-induced signal transduction, gene expression, and antitumor activity of immune effector cells are negatively regulated by suppressor of cytokine signaling proteins. J Immunol. 2007; 178: 4832-4845. Ref.: https://goo.gl/dbBKpi
  29. Rakesh K, Agrawal DK. Controlling cytokine signaling by constitutive inhibitors. Biochem Pharmacol. 2005; 70: 649-657. Ref.: https://goo.gl/Nx1qyY
  30. Win-Piazza H, Schneeberger V, Chen L, Pernazza D, Lawrence HR, et al. Enhanced anti-melanoma efficacy of interferon alfa-2b via inhibition of Shp2. Cancer Letters. 2012. Ref.: https://goo.gl/hSHCEr
  31. Hu S, Xie Z, Onishi A, Yu X, Jiang L, et al. Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling. Cell. 2009; 139: 610-622. Ref.: https://goo.gl/m8xSwO
  32. Bhattacharya S, Zheng H, Tzimas C, Carroll M, Baker DP, et al. Bcr-abl signals to desensitize chronic myeloid leukemia cells to IFNalpha via accelerating the degradation of its receptor. Blood. 2011; 118: 4179-4187. Ref.: https://goo.gl/bzU6Je
  33. Huangfu WC, Qian J, Liu C, Liu J, Lokshin AE, et al. Inflammatory signaling compromises cell responses to interferon alpha. Oncogene. 2012; 31: 161-172. Ref.: https://goo.gl/kvAocc
  34. Einat M, Resnitzky D, Kimchi A. Close link between reduction of c-myc expression by interferon and, G0/G1 arrest. Nature. 1985; 313: 597-600. Ref.: https://goo.gl/ur2eET
  35. Tiefenbrun N, Melamed D, Levy N, Resnitzky D, Hoffman I, et al. Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest. Mol Cell Biol. 1996; 16: 3934-3944. Ref.: https://goo.gl/X8G8jM
  36. Petricoin EF, Ito S, Williams BL, Audet S, Stancato LF, et al. Antiproliferative action of interferon-alpha requires components of T-cell-receptor signalling. Nature. 1997; 390: 629-632. Ref.: https://goo.gl/drvaWw
  37. Kalie E, Jaitin DA, Abramovich R, Schreiber G. An interferon α2 mutant optimized by phage display for IFNAR1 binding confers specifically enhanced antitumor activities. J Biol Chem. 2007; 282: 11602-11611. Ref.: https://goo.gl/oCG5pn
  38. Thomas C, Moraga I, Levin D, Krutzik PO, Podoplelova Y, et al. Structural linkage between ligand discrimination and receptor activation by type I interferons. Cell. 2011; 146: 621-632. Ref.: https://goo.gl/rErOrF
  39. Lim R, Knight B, Patel K, McHutchison JG, Yeoh GC, et al. Antiproliferative effects of interferon alpha on hepatic progenitor cells in vitro and in vivo. Hepatology. 2006; 43: 1074-1083. Ref.: https://goo.gl/CMOGx5
  40. Yang G, Xu Y, Chen X, Hu G. IFITM1 plays an essential role in the antiproliferative action of interferon-gamma. Oncogene. 2007; 26: 594-603. Ref.: https://goo.gl/WEaP9d
  41. Bailey CM, Abbott DE, Margaryan NV, Khalkhali-Ellis Z, Hendrix MJ. Interferon regulatory factor 6 promotes cell cycle arrest and is regulated by the proteasome in a cell cycle-dependent manner. Mol Cell Biol. 2008; 28: 2235-2243. Ref.: https://goo.gl/gwHuHT
  42. Hosono T, Tanaka T, Tanji K, Nakatani T, Kamitani T. NUB1, an interferon-inducible protein, mediates anti-proliferative actions and apoptosis in renal cell carcinoma cells through cell-cycle regulation. Br J Cancer. 2010; 102: 873-882. Ref.: https://goo.gl/QkTCX6
  43. Vitale G, Zappavigna S, Marra M, Dicitore A, Meschini S, et al. The PPAR-gamma agonist troglitazone antagonizes survival pathways induced by STAT-3 in recombinant interferon-beta treated pancreatic cancer cells. Biotechnol Adv. 2012; 30: 169-184. Ref.: https://goo.gl/NkOSjx
  44. Shin EC, Ahn JM, Kim CH, Choi Y, Ahn YS, et al. IFN-gamma induces cell death in human hepatoma cells through a TRAIL/death receptor-mediated apoptotic pathway. Int J Cancer. 2001; 93: 262-268. Ref.: https://goo.gl/u6Uakl
  45. Carillo MC, Alvarez Mde L, Quiroga AD. Interferon alfa-2b triggers transforming growth factor-beta-induced apoptosis on preneoplasticliver. Ann Hepatol. 2006; 5: 244-250. Ref.: https://goo.gl/wJwZ1y
  46. Pokrovskaja K, Panaretakis T, Grander D. Alternative signaling pathways regulating type I interferon-induced apoptosis. J Interferon Cytokine Res. 2005; 25: 799-810. Ref.: https://goo.gl/iQfd8X
  47. Yin H, Xie F, Zhang J, Yang Y, Deng B, et al. Combination of interferon-alpha and 5-fluorouracil induces apoptosis through mitochondrial pathway in hepatocellular carcinoma in vitro. Cancer Lett. 2011; 306: 34-42. Ref.: https://goo.gl/C8Rroy
  48. Dal Col J, Mastorci K, Fae DA, Muraro E, Martorelli D, et al. Alpha-interferon/retinoic acid combination inhibits growth and promotes apoptosis in mantle cell lymphoma through Akt-dependent modulation of critical targets. Cancer Res. 2012. Ref.: https://goo.gl/qJB1vX
  49. Sun L, Wang H, Wang Z, He S, Chen S, et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012; 148: 213-227. Ref.: https://goo.gl/8IQNiG
  50. Wang Z, Jiang H, Chen S, Du F, Wang X. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell. 2012; 148: 228-243. Ref.: https://goo.gl/ZLoEWl
  51. Robinson N, McComb S, Mulligan R, Dudani R, Krishnan L, et al. Type I interferon induces necroptosis in macrophages during infection with Salmonella enterica serovar Typhimurium. Nat Immunol. 2012; 13: 954-962. Ref.: https://goo.gl/ya1cHa
  52. Li P, Du Q, Cao Z, Guo Z, Evankovich J, et al. Interferon-gamma induces autophagy with growth inhibition and cell death in human hepatocellular carcinoma (HCC) cells through interferon-regulatory factor-1 (IRF-1). Cancer Lett. 2012; 314: 213-222. Ref.: https://goo.gl/Qzcxfy
  53. Chiantore MV, Vannucchi S, Accardi R, Tommasino M, Percario ZA, et al. Interferon-beta induces cellular senescence in cutaneous human papilloma virus-transformed human keratinocytes by affecting p53 transactivating activity. PloS One. 2012; 7: e36909. Ref.: https://goo.gl/YP7m9u
  54. Ben Reguiga M, Bouquet C, Farinotti R, Bonhomme-Faivre L. Interferon-alpha improves docetaxel antitumoral and antimetastatic efficiency in Lewis lung carcinoma bearing mice. Life Sci. 2012; 91: 843-851. Ref.: https://goo.gl/FeRtGS
  55. Cheng X, Liu Y, Chu H, Kao HY. Promyelocytic leukemia protein (PML) regulates endothelial cell network formation and migration in response to tumor necrosis factor alpha (TNFalpha) and interferon alpha (IFNalpha). J Biol Chem. 2012; 287: 23356-23367. Ref.: https://goo.gl/k0t6LI
  56. Hudak L, Tezeeh P, Wedel S, Makarevic J, Juengel E, et al. Low dosed interferon alpha augments the anti-tumor potential of histone deacetylase inhibition on prostate cancer cell growth and invasion. Prostate. 2012; 72: 1719-1735. Ref.: https://goo.gl/2qdDe3
  57. Rosewicz S, Detjen K, Scholz A, von Marschall Z. Interferon-alpha: regulatory effects on cell cycle and angiogenesis. Neuroendocrinology. 2004; 80: 85-93. Ref.: https://goo.gl/HaaT85
  58. Indraccolo S, Tisato V, Tosello V, Habeler W, Esposito G, et al. Interferon-alpha gene therapy by lentiviral vectors contrasts ovarian cancer growth through angiogenesis inhibition. Hum Gene Ther. 2005; 16: 957-970. Ref.: https://goo.gl/i2F1GS
  59. Yoshiji H, Noguchi R, Kuriyama S, Yoshii J, Ikenaka Y. Combination of interferon and angiotensin-converting enzyme inhibitor, perindopril, suppresses liver carcinogenesis and angiogenesis in mice. Oncol Rep. 2005; 13: 491-495. Ref.: https://goo.gl/91pqpe
  60. Lee J, Wang A, Hu Q, Lu S, Dong Z. Adenovirus-mediated interferon-beta gene transfer inhibits angiogenesis in and progression of orthotopic tumors of human prostate cancer cells in nude mice. Int J Oncol. 2006; 29: 1405-1412. Ref.: https://goo.gl/bUIiay
  61. Lee JH, Chun T, Park SY, Rho SB. Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs. Biochim Biophys. 2008; 1783: 1654-1662. Ref.: https://goo.gl/DDPE23
  62. Wang M, Zhang J, Wu X, Jin X, Zhao B, et al. Discovery of a pyrazole derivative promoting angiogenesis through modulating reactive oxygen species and interferon-inducible protein 10 levels. Mol Biol Rep. 2011; 38: 1491-1497. Ref.: https://goo.gl/tSEkZh
  63. Xiao HB, Zhou WY, Chen XF, Mei J, Lv ZW, et al. Interferon-beta efficiently inhibited endothelial progenitor cell-induced tumor angiogenesis. Gene Ther. 2012. 19: 1030-1034. Ref.: https://goo.gl/Qk5VdO
  64. Zheng H, Qian J, Carbone CJ, Leu NA, Baker DP, et al. Vascular endothelial growth factor-induced elimination of the type 1 interferon receptor is required for efficient angiogenesis. Blood. 2011; 118: 4003-4006. Ref.: https://goo.gl/MdNm02
  65. Xiao HB, Zhou WY, Chen XF, Mei J, Lv ZW, et al. Interferon-beta efficiently inhibited endothelial progenitor cell-induced tumor angiogenesis. Gene Ther. 2012; 19: 1030-1034. Ref.: https://goo.gl/21ZLFU
  66. Palmer KJ, Harries M, Gore ME, Collins MK. Interferon-alpha (IFN-alpha) stimulates anti-melanoma cytotoxic T lymphocyte (CTL) generation in mixed lymphocyte tumour cultures (MLTC). Clin Exp Immunol. 2000; 119: 412-418. Ref.: https://goo.gl/sj7Khn
  67. Lombardi G, Dunne PJ, Scheel-Toellner D, Sanyal T, Pilling D, et al. Type 1 IFN maintains the survival of anergic CD4+ T cells. J Immunol. 2000; 165: 3782-3789. Ref.: https://goo.gl/8DN08B
  68. Marrack P, Kappler J, Mitchell T. Type I interferons keep activated T cells alive. J Exp Med. 1999; 189: 521-530. Ref.: https://goo.gl/lztwR2
  69. Fleetwood AJ, Dinh H, Cook AD, Hertzog PJ, Hamilton JA. GM-CSF- and M-CSF-dependent macrophage phenotypes display differential dependence on type I interferon signaling. J Leukoc Biol. 2009; 86: 411-421. Ref.: https://goo.gl/7ZUudm
  70. Frendeus KH, Wallin H, Janciauskiene S, Abrahamson M. Macrophage responses to interferon-gamma are dependent on cystatin C levels. Int J Biochem Cell Biol. 2009; 41: 2262-2269. Ref.: https://goo.gl/ApxJYn
  71. Lin AA, Tripathi PK, Sholl A, Jordan MB, Hildeman DA. Gamma interferon signaling in macrophage lineage cells regulates central nervous system inflammation and chemokine production. J Virol. 2009; 83: 8604-8615. Ref.: https://goo.gl/0Zdcgf
  72. Reiter Z. Interferon--a major regulator of natural killer cell-mediated cytotoxicity. J Interferon Res. 1993; 13: 247-257. Ref.: https://goo.gl/VC6wpg
  73. Tian P, Lin T, Hong J, Zhang Q, Wu H, Yu X, et al. 2′-5′P3A3 can enhance the activity of natural killer cells (in Chinese). Chinese Journal of Cell Biology. 1984; 6: 36-39.
  74. Nakajima H, Oka Y, Tsuboi A, Tatsumi N, Yamamoto Y, et al. Enhanced tumor immunity of WT1 peptide vaccination by interferon-beta administration. Vaccine. 2012; 30: 722-729. Ref.: https://goo.gl/RwI0V7
  75. Fuertes MB, Kacha AK, Kline J, Woo SR, Kranz DM, et al. Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8{alpha}+dendritic cells. J Exp Med. 2011; 208: 2005-2016. Ref.: https://goo.gl/9XH5rN
  76. Chen J, Feng Y, Lu L, Wang H, Dai L, Li Y, et al. Interferon-gamma-induced PD-L1 surface expression on human oral squamous carcinoma via PKD2 signal pathway. Immunobiology. 2012; 217: 385-393. Ref.: https://goo.gl/8RxvpV
  77. Yang YQ, Dong WJ, Yin XF, Xu YN, Yang Y, et al. Interferon-related secretome from direct interaction between immune cells and tumor cells is required for upregulation of PD-L1 in tumor cells. Protein Cell. 2016; 7: 538-543. Ref.: https://goo.gl/bQQnb3
  78. Benci JL, Xu B, Qiu Y, Wu TJ, Dada H, et al. Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade. Cell. 2016; 167: 1540-1554. Ref.: https://goo.gl/JbHDgv
  79. Mocellin S, Pasquali S, Rossi CR, Nitti D. Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis. J Natl Cancer Inst. 2010; 102: 493-501. Ref.: https://goo.gl/ncTijO
  80. Naoe M, Ogawa Y, Hasebe Y, Morita J, Shichijo T, et al. Enhancement of IL-2-induced cytotoxicity by interferon-alpha in renal cell carcinoma. Oncol Res. 2011; 19: 479-486. Ref.: https://goo.gl/HNLPC1
  81. Kasai K, Ushio A, Kasai Y, Sawara K, Miyamoto Y, et al. Therapeutic efficacy of combination therapy with intra-arterial 5-fluorouracil and systemic pegylated interferon alpha-2b for advanced hepatocellular carcinoma with portal venous invasion. Cancer. 2012; 118: 3302-3310. Ref.: https://goo.gl/fMoxVY
  82. Khallouf H, Marten A, Serba S, Teichgraber V, Buchler MW, et al. 5-Fluorouracil and Interferon-alpha Immunochemotherapy Enhances Immunogenicity of Murine Pancreatic Cancer Through Upregulation of NKG2D Ligands and MHC Class I. J Immunother. 2012; 35: 245-253. Ref.: https://goo.gl/CmhIzB
  83. ishman AI, Johnson B, Alexander B, Won J, Choudhury M, et al. Additively enhanced antiproliferative effect of interferon combined with proanthocyanidin on bladder cancer cells. J Cancer. 2012; 3: 107-112. Ref.: https://goo.gl/RfFlqq
  84. Armstrong L, Arrington A, Han J, Gavrikova T, Brown E, et al. Generation of a novel, cyclooxygenase-2-targeted, interferon-expressing, conditionally replicative adenovirus for pancreatic cancer therapy. Am J surg. 2012; 204: 741-750. Ref.: https://goo.gl/z5P3dr
  85. Armstrong L, Davydova J, Brown E, Han J, Yamamoto M, et al. Delivery of interferon alpha using a novel Cox2-controlled adenovirus for pancreatic cancer therapy. Surgery. 2012; 152: 114-122. Ref.: https://goo.gl/N96rR9
  86. Huang H, Xiao T, He L, Ji H, Liu XY. Interferon-beta-armed oncolytic adenovirus induces both apoptosis and necroptosis in cancer cells. Acta Biochimi Biophys Sin. 2012; 44: 737-745. Ref.: https://goo.gl/JGQKIX
  87. He LF, Wang YG, Xiao T, Zhang KJ, Li GC, et al. Suppression of cancer growth in mice by adeno-associated virus vector-mediated IFN-beta expression driven by hTERT promoter. Cancer Lett. 2009; 286: 196-205. Ref.: https://goo.gl/fKlXbt
  88. Pockros PJ. Why do we need another interferon? Gastroenterology. 2010; 139: 1084-1086. Ref.: https://goo.gl/S1437v
  89. Talpaz M, Hehlmann R, Quintas-Cardama A, Mercer J, Cortes J. Re-emergence of interferon-alpha in the treatment of chronic myeloid leukemia. Leukemia. 2013; 27: 803-812. Ref.: https://goo.gl/PcWCOC
  90. Kose S, Gozaydin A, Akkoclu G, Ece G. Chronic hepatitis B with type I diabetes mellitus and autoimmune thyroiditis development during interferon alpha therapy. J Infect Dev Ctries. 2012; 6: 364-368. Ref.: https://goo.gl/JjOqjY
  91. Akeno N, Smith EP, Stefan M, Huber AK, Zhang W, et al. IFN-α mediates the development of autoimmunity both by direct tissue toxicity and through immune cell recruitment mechanisms. J Immunol. 2011; 186: 4693-706. Ref.: https://goo.gl/GkF94w
  92. Stefan M, Jacobson EM, Huber AK, Greenberg DA, Li CW, et al. Novel variant of thyroglobulin promoter triggers thyroid autoimmunity through an epigenetic interferon α-modulated mechanism. J Biol Chem. 2011; 286: 31168-79. Ref.: https://goo.gl/X2eujT
  93. Stefan M, Wei C, Lombardi A, Li CW, Concepcion ES, et al. Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity. Pro Natl Acad Sci. 2014; 111: 12562-7. Ref.: https://goo.gl/mi7kBJ
  94. Lombardi A, Tomer Y. Interferon alpha impairs insulin production in human beta cells via endoplasmic reticulum stress. J Autoimmun. 2017. Ref.: https://goo.gl/0g7JX3
  95. Wang YX, Jiang CL, Lu CL, Song LX, You ZD, et al. Distinct domains of IFNalpha mediate immune and analgesic effects respectively. J Neuroimmunol. 2000; 108: 64-67. Ref.: https://goo.gl/bReYTV
  96. Jiang CL, Son LX, Lu CL, You ZD, Wang YX, et al. Analgesic effect of interferon-alpha via mu opioid receptor in the rat. Neurochem Int. 2000; 36: 193-196. Ref.: https://goo.gl/GKdlIY
  97. Wang YX, Xu WG, Sun XJ, Chen YZ, Liu XY, et al. Fever of recombinant human interferon-alpha is mediated by opioid domain interaction with opioid receptor inducing prostaglandin E2. J Neuroimmunol. 2004; 156: 107-112. Ref.: https://goo.gl/OqlJdG
  98. Liu B, Liao J, Rao X, Kushner SA, Chung CD, et al. Inhibition of Stat1-mediated gene activation by PIAS1. Proc Natl Acad Sci U S A. 1998; 95: 10626-10631. Ref.: https://goo.gl/5KOmO3
  99. Larner AC, Petricoin EF, Nakagawa Y, Finbloom DS. IL-4 attenuates the transcriptional activation of both IFN-alpha and IFN-gamma-induced cellular gene expression in monocytes and monocytic cell lines. J Immunol. 1993; 150: 1944-1950. Ref.: https://goo.gl/TVQfSy
  100. Ito S, Ansari P, Sakatsume M, Dickensheets H, Vazquez N, et al. Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma- induced genes by suppressing tyrosine phosphorylation of STAT1. Blood. 1999; 93: 1456-1463. Ref.: https://goo.gl/nO5yul
  101. Park IK, Shultz LD, Letterio JJ, Gorham JD. TGF-beta1 inhibits T-bet induction by IFN-gamma in murine CD4+ T cells through the protein tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1. J Immunol. 2005; 175: 5666-5674. Ref.: https://goo.gl/g7ROyO
  102. Viguier M, Lemaitre F, Verola O, Cho MS, Gorochov G, et al. Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J Immunol. 2004; 173: 1444-1453. Ref.: https://goo.gl/4bgT5q
  103. Serafini P, Borrello I, Bronte V. Myeloid suppressor cells in cancer: recruitment, phenotype, properties, and mechanisms of immune suppression. Semin Cancer Biol. 2006; 16: 53-65. Ref.: https://goo.gl/ZZOzjC
  104. Gabrilovich D, Ishida T, Oyama T, Ran S, Kravtsov V, et al. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood. 1998; 92: 4150-4166. Ref.: https://goo.gl/LeJe66
  105. Katlinski KV, Gui J, Katlinskaya YV, Ortiz A, Chakraborty R, et al. Inactivation of Interferon Receptor Promotes the Establishment of Immune Privileged Tumor Microenvironment. Cancer Cell. 2017; 31: 194-207. Ref.: https://goo.gl/jp6uXg
  106. Bernabei P, Bosticardo M, Losana G, Regis G, Di Paola F, et al. IGF-1 down-regulates IFN-gamma R2 chain surface expression and desensitizes IFN-gamma/STAT-1 signaling in human T lymphocytes. Blood. 2003; 102: 2933-2939. Ref.: https://goo.gl/7TuSgQ
  107. Subramanian GM, Fiscella M, Lamouse-Smith A, Zeuzem S, McHutchison JG. Albinterferon alpha-2b: a genetic fusion protein for the treatment of chronic hepatitis C. Nat Biotechnol. 2007; 25: 1411-1419. Ref.: https://goo.gl/bkb2VO
  108. Miller DM, Klucher KM, Freeman JA, Hausman DF, Fontana D, et al. Interferon lambda as a potential new therapeutic for hepatitis C. Ann N Y Acad Sci. 2009; 1182: 80-87. Ref.: https://goo.gl/ldK2yV
  109. Ceaglio N, Etcheverrigaray M, Conradt HS, Grammel N, Kratje R, et al. Highly glycosylated human alpha interferon: An insight into a new therapeutic candidate. J Biotechnol. 2010; 146: 74-83. Ref.: https://goo.gl/5rQpRd
  110. Xuan C, Steward KK, Timmerman JM, Morrison SL. Targeted delivery of interferon-alpha via fusion to anti-CD20 results in potent antitumor activity against B-cell lymphoma. Blood. 2010; 115: 2864-2871. Ref.: https://goo.gl/EBTB8A
  111. Yin XF, Yang YQ, Li HL, Xu YN, Chen LY, et al. A potent in vivo anti-tumor efficacy of novel recombinant type I interferon. Clin Cancer Res. 2017; 23: 2038-2049. Ref.: https://goo.gl/pU3Flg


Figure 1

Figure 1

Figure 1

Figure 2

Similar Articles

Recently Viewed

  • Cleat-surface Interface and Lower Extremity Injuries
    Ryann Davie*, Brittany Ammerman and Natalie Pahapill and Karen Sutton Ryann Davie*, Brittany Ammerman, Natalie Pahapill and Karen Sutton. Cleat-surface Interface and Lower Extremity Injuries. J Sports Med Ther. 2023: doi: 10.29328/journal.jsmt.1001071; 8: 047-050
  • Atopic Conjunctivitis in Children: Influence of Treatment with Topical Cyclosporin 0.05% in the Quality of Life
    Carlos Alberto Sánchez Salguero* and Álvaro Isidro Sánchez Chacón Carlos Alberto Sánchez Salguero*,Álvaro Isidro Sánchez Chacón. Atopic Conjunctivitis in Children: Influence of Treatment with Topical Cyclosporin 0.05% in the Quality of Life . Arch Asthma Allergy Immunol. 2017: doi: 10.29328/journal.haard.1001001; 1: 001-008
  • Community, health and rehabilitation
    Alessandro Giustini* Alessandro Giustini*. Community, health and rehabilitation. J Community Med Health Solut. 2023: doi: 10.29328/journal.jcmhs.1001025; 4: 001-003
  • Control of arterial hypertension and risk of new-onset of atrial fibrillation in patients with metabolic syndrome
    Ylber Jani*, Kastriot Haxhirexha, Ferizat Haxhirexha, Bekim Pocesta, Atila Rexhepi, Fatmir Ferati, Ahmet Kamberi, Agim Zeqiri, Sotiraq Xhunga, Artur Serani and Lutfi Zylbeari Ylber Jani*,Kastriot Haxhirexha,Ferizat Haxhirexha,Bekim Pocesta,Atila Rexhepi,Fatmir Ferati,Ahmet Kamberi,Agim Zeqiri,Sotiraq Xhunga,Artur Serani,Lutfi Zylbeari. Control of arterial hypertension and risk of new-onset of atrial fibrillation in patients with metabolic syndrome. J Cardiol Cardiovasc Med. 2022: doi: 10.29328/journal.jccm.1001126; 7: 017-022
  • Fever of Unknown Origin in Children: The Challenge of History Taking
    S Testa, S Faranghi, S Mazzitelli, GB Beretta, G Di Pietro, G Renisi and Antonella Petaccia* S Testa, S Faranghi, S Mazzitelli, GB Beretta, G Di Pietro, G Renisi, Antonella Petaccia*. Fever of Unknown Origin in Children: The Challenge of History Taking. Arch Case Rep. 2023: doi: 10.29328/journal.acr.1001081; 7: 062-065

Read More

Most Viewed

Read More

Help ?