Interferon-related signaling pathways and clinical application in tumor therapy

Abstract

Abstract:

Type Ⅰ, Ⅱ, Ⅲ interferons have anti-tumor potential, but the mechanism of action and clinical effect are different. Signaling pathways associated with interferon-treated tumors mainly include JAK-STAT, PI3K/AKT/mTOR, MAPK, NF-κB, c-Abl,etc. Type Ⅰ interferon has the widest clinical application and the most definite curative effect at present. Because of its serious adverse reaction and possible role in the process of cancer induction, type Ⅱ interferon has a great controversy on whether it can be used in anti-tumor therapy. The biological function of type Ⅲ interferon has good characteristics of type Ⅰ and Ⅱ interferon, but its anti-tumor medicinal value needs to be further evaluated.

Key words:Interferons,Neoplasms,Signal pathway,Clinical trial

Li Yuxiang, Wang Xinwen. Interferon-related signaling pathways and clinical application in tumor therapy[J]. Journal of International Oncology, 2020, 47(6): 364-367.

References27

[1]	Rentiya ZS, Wells M, Bae J, et al. Interferon-α-induced retinopathy in chronic hepatitis C treatment: summary, considerations, and recommendations[J]. Graefes Arch Clin Exp Ophthalmo, 2019,257(3):447-452. DOI: 10.1007/s00417-018-04209-7. doi:10.1007/s00417-018-04209-7
[2]	Sceneay J, Goreczny GJ, Wilson K, et al. Interferon signaling is diminished with age and is associated with Immune checkpoint blockade efficacy in triple-negative breast cance[J]. Cancer Discov, 2019,9(9):1208-1227. DOI: 10.1158/2159-8290.CD-18-1454. doi:10.1158/2159-8290.CD-18-1454pmid:31217296
[3]	Lasfar A, Gogas H, Zloza A, et al. IFN-λ cancer immunotherapy: new kid on the block[J]. Immunotherapy, 2016,8(8):877-888. DOI: 10.2217/imt-2015-0021. doi:10.2217/imt-2015-0021pmid:27381684
[4]	Mitchell S, Mercado EL, Adelaja A, et al. An NFκB activity calculator to delineate signaling crosstalk: type Ⅰ and Ⅱ interferons enhance NFκB via distinct mechanisms[J]. Front Immunol, 2019,10:1425. DOI: 10.3389/fimmu.2019.01425. doi:10.3389/fimmu.2019.01425pmid:31293585
[5]	Mojic M, Takeda K, Hayakawa Y. The dark side of IFN-γ: its role in promoting cancer immunoevasion[J]. Int J Mol Sci, 2017, 19(1). pii: E89. DOI: 10.3390/ijms19010089. pmid:29351251
[6]	Ni L, Lu J. Interferon gamma in cancer immunotherapy[J]. Cancer Med, 2018,7(9):4509-4516. DOI: 10.1002/cam4.1700. doi:10.1002/cam4.1700pmid:30039553
[7]	O'Brien TR, Young HA, Donnelly RP, et al. Meeting overview: interferon lambda-disease impact and therapeutic potential[J]. J Interferon Cytokine Res, 2019,39(10):586-591. DOI: 10.1089/jir.2019.0018. doi:10.1089/jir.2019.0018pmid:30998425
[8]	Lazear HM, Schoggins JW, Diamond MS. Shared and distinct functions of type Ⅰ and type Ⅲ interferons[J]. Immunity, 2019,50(4):907-923. DOI: 10.1016/j.immuni.2019.03.025. doi:10.1016/j.immuni.2019.03.025pmid:30995506
[9]	Zhao Q, Cheng W, Xi Y, et al. IFN-β regulates Th17 differentiation partly through the inhibition of osteopontin in experimental autoimmune encephalomyelitis[J]. Mol Immunol, 2018,93:20-30. DOI: 10.1016/j.molimm.2017.11.002. doi:10.1016/j.molimm.2017.11.002pmid:29127843
[10]	Bhat MY, Solanki HS, Advani J, et al. Comprehensive network map of interferon gamma signaling[J]. J Cell Commun Signal, 2018,12(4):745-751. DOI: 10.1007/s12079-018-0486-y. doi:10.1007/s12079-018-0486-ypmid:30191398
[11]	Cheon H, Yang J, Stark GR. The functions of signal transducers and activators of transcriptions 1 and 3 as cytokine-inducible proteins[J]. J Interferon Cytokine Res, 2011,31(1):33-40. DOI: 10.1089/jir.2010.0100. doi:10.1089/jir.2010.0100pmid:21166594
[12]	Yeh YH, Hsiao HF, Yeh YC, et al. Inflammatory interferon activates HIF-1α-mediated epithelial-to-mesenchymal transition via PI3K/AKT/mTOR pathway[J]. J Exp Clin Cancer Res, 2018,37(1):70. DOI: 10.1186/s13046-018-0730-6. doi:10.1186/s13046-018-0730-6pmid:29587825
[13]	Al-Attar R, Childers CL, Nguyen VC, et al. Differential protein phosphorylation is responsible for hypoxia-induced regulation of the Akt/mTOR pathway in naked mole rats[J]. Comp Biochem Physiol A Mol Integr Physiol, 2020,242:110653. DOI: 10.1016/j.cbpa.2020.110653. doi:10.1016/j.cbpa.2020.110653pmid:31926299
[14]	Ma RJ, Tan YQ, Zhou G, et al. Aberrant IGF1-PI3K/AKT/MTOR signaling pathway regulates the local immunity of oral lichen planus[J]. Immunobiology, 2019,224(3):455-461. DOI: 10.1016/j.imbio.2019.01.004. doi:10.1016/j.imbio.2019.01.004pmid:30773287
[15]	梁木林, 党红星, 鲁雪, 等. 抑制mTOR信号通路对幼鼠肺损伤时p-AKT1分子的影响及意义[J]. 中国病理生理杂志, 2019,35(3):506-514. DOI: 10.3969/j.issn.1000-4718.2019.03.021.
[16]	Wang H, Wang J, Shi X, et al. Genetically engineered bone marrow-derived mesenchymal stem cells co-expressing IFN-γ and IL-10 inhibit hepatocellular carcinoma by modulating MAPK pathway[J]. J BUON, 2017,22(6):1517-1524. pmid:29332347
[17]	Valledor AF, Sánchez-Tilló E, Arpa L, et al. Selective roles of MAPKs during the macrophage response to IFN-gamma[J]. J Immunol, 2008,180(7):4523-4529. DOI: 10.4049/jimmunol.180.7.4523. doi:10.4049/jimmunol.180.7.4523pmid:18354174
[18]	Truong AD, Hong Y, Hoang CT, et al. Chicken IL-26 regulates immune responses through the JAK/STAT and NF-κB signaling pathways[J]. Dev Comp Immunol, 2017,73:10-20. DOI: 10.1016/j.dci.2017.03.001. doi:10.1016/j.dci.2017.03.001pmid:28259699
[19]	Ning L, Huang X, Xu Y, et al. Boosting of hepatitis B virus-specific T cell responses after pegylated-interferon-alpha-2a therapy for hepatitis B e antigen-positive pediatric patients[J]. J Interferon Cytokine Res, 2019,39(12):740-751. DOI: 10.1089/jir.2019.0042. doi:10.1089/jir.2019.0042pmid:31329012
[20]	Suzuki T, Sakata K, Mizuno N, et al. Different involvement of the MAPK family in inflammatory regulation in human pulmonary microvascular endothelial cells stimulated with LPS and IFN-gamma[J]. Immunobiology, 2018,223(12):777-785. DOI: 10.1016/j.imbio.2018.08.003. doi:10.1016/j.imbio.2018.08.003pmid:30115376
[21]	Suarez-Kelly LP, Levine KM, Olencki TE, et al. A pilot study of interferon-alpha-2b dose reduction in the adjuvant therapy of high-risk melanoma[J]. Cancer Immunol Immunother, 2019,68(4):619-629. DOI: 10.1007/s00262-019-02308-w. doi:10.1007/s00262-019-02308-wpmid:30725205
[22]	Lowenstein A, Fainboim H, Reyes A, et al. Autoimmune and non-autoimmune thyroid dysfunction in HCV infected and HCV-HIV co-infected patients before and after interferon alpha therapy: a prospective study[J]. Endocrinol Diabetes Nutr, 2019. pii: S2530-0164(19)30144-2. DOI: 10.1016/j.endinu.2019.04.012. doi:10.1016/j.endinu.2020.01.006pmid:32499203
[23]	Ding GQ, Yu YL, Shen ZJ, et al. Antitumor effects of human interferon-alpha 2b secreted by recombinant bacillus Calmette-Guérin vaccine on bladder cancer cells[J]. J Zhejiang Univ Sci B, 2012,13(5):335-341. DOI: 10.1631/jzus.B1100366. doi:10.1631/jzus.B1100366pmid:22556170
[24]	Liu Y, Liu G, Liu Q, et al. The cellular character of liquefaction degeneration in oral lichen planus and the role of interferon gamma[J]. J Oral Pathol Med, 2017,46(10):1015-1022. DOI: 10.1111/jop.12595. doi:10.1111/jop.12595pmid:28556960
[25]	Lv N, Gao Y, Guan H, et al. Inflammatory mediators, tumor necrosis factor-α and interferon-γ, induce EMT in human PTC cell lines[J]. Oncol Lett, 2015,10(4):2591-2597. DOI: 10.3892/ol.2015.3518. doi:10.3892/ol.2015.3518pmid:26622895
[26]	Gao D, Yu X, Zhang B, et al. Role of autophagy in inhibiting the proliferation of A549 cells by type Ⅲ interferon[J]. Cell Biol Int, 2019,43(6):605-612. DOI: 10.1002/cbin.11132. doi:10.1002/cbin.11132pmid:30958598
[27]	Choobin H, Bamdad T, Soleimanjahi H, et al. Antitumor effect of mIFN-lambda3 in C57BL/6 mice model for papilloma tumors[J]. Mol Biol (Mosk), 2015,49(5):777-784. DOI: 10.7868/S0026898415050067.