medigraphic.com
ISSN 2395-8723 (Digital)
ISSN 1405-888X (Impreso)
TIP Revista Especializada en Ciencias Químico-Biológicas

2023, Número 1

<< Anterior Siguiente >>

TIP Rev Esp Cienc Quim Biol 2023; 26 (1)


Interferón-gamma: vías de señalización y sus implicaciones en el cáncer

Zamora-Salas SX, Robles-Villarruel ML, Macías-Silva M, Álvarez-Sánchez ME, Tecalco-Cruz ÁC

Idioma: Español
Referencias bibliográficas: 84
Paginas: 1-17
Archivo PDF: 662.66 Kb.


RESUMEN

Los interferones son una familia de proteínas involucradas en actividades antivirales, inmunomoduladoras y antiinflamatorias. En los últimos años, su estudio se ha incrementado en el contexto del cáncer, y uno de los hallazgos más importantes es que son parte del microambiente de los tumores. El interferón-gamma (IFN-γ) es uno de los miembros de la familia de los interferones y tiene funciones protumorales o antitumorales dependiendo del tipo de cáncer y del microambiente tumoral. En esta revisión se discuten los elementos de la vía de transducción de señales canónica del IFN-γ y sus implicaciones en el desarrollo de las neoplasias malignas. Los estudios sugieren que los elementos de la vía activada por el IFN-γ podrían ser útiles como biomarcadores y/o como blanco de terapias para el cáncer.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Abou El Hassan, M., Huang, K., Eswara, M. B. K., Xu, Z., Yu,T., Aubry, A., Ni, Z., Livne-bar, I., Sangwan, M., Ahmad,M. & Bremner, R. (2017). Properties of STAT1 and IRF1enhancers and the influence of SNPs. BMC MolecularBiology, 18(1), 1–19. https://doi.org/10.1186/s12867-017-0084-1

  2. Alavi, S., Stewart, A. J., Kefford, R. F., Lim, S. Y., Shklovskaya,E. & Rizos, H. (2018). Interferon signaling is frequentlydownregulated in melanoma. Frontiers in Immunology,9(1414). https://doi.org/10.3389/fimmu.2018.01414

  3. Alhawamdeh, M., Isreb, M., Aziz, A., Jacob, B. K., Anderson,D. & Najafzadeh, M. (2021). Interferon-γ liposome: A newsystem to improve drug delivery in the treatment of lungcancer. ERJ Open Research, 7(2000555). https://doi.org/10.1183/23120541.00555-2020

  4. Alsamman, K. & El-Masry, O. S. (2018). Interferon regulatoryfactor 1 inactivation in human cancer. Bioscience Reports,38(3), 1–14. https://doi.org/10.1042/BSR20171672

  5. Alshaker, H. A. & Matalka, K. Z. (2011). IFN-γ, IL-17 and TGF-βinvolvement in shaping the tumor microenvironment: Thesignificance of modulating such cytokines in treatingmalignant solid tumors. Cancer Cell International, 11(1),33. https://doi.org/10.1186/1475-2867-11-33

  6. Alspach, E., Lussier, D. M. & Schreiber, R. D. (2019). Interferonγ and Its Important Roles in Promoting and InhibitingSpontaneous and Therapeutic Cancer Immunity. ColdSpring Harbor Perspectives in Biology, 11(3), a028480.

  7. Angelicola, S., Ruzzi, F., Landuzzi, L., Scalambra, L.,Gelsomino, F., Ardizzoni, A., Nanni, P., Lollini, P. L. &Palladini, A. (2021). IFN-γ and CD38 in hyperprogressivecancer development. Cancers, 13(2), 1–25. https://doi.org/10.3390/cancers13020309

  8. Bach, E. A., Aguet, M. & Schreiber, R. D. (1997). The IFNγreceptor: A paradigm for cytokine receptor signaling.Annual Review of Immunology, 15, 563–591. https://doi.org/10.1146/annurev.immunol.15.1.563

  9. Bach, E. A., Tanner, J. W., Marsters, S., Ashkenazi, A., Aguet,M., Shaw, A. S. & Schreiber, R. D. (1996). Ligand-inducedassembly and activation of the gamma interferon receptorin intact cells. Molecular and Cellular Biology, 16(6),3214–3221. https://doi.org/10.1128/mcb.16.6.3214

  10. Balandeh, E., Mohammadshafie, K., Mahmoudi, Y., HosseinPourhanifeh, M., Rajabi, A., Bahabadi, Z. R., Mohammadi,A. H., Rahimian, N., Hamblin, M. R. & Mirzaei, H.(2021). Roles of non-coding RNAs and angiogenesisin glioblastoma. Frontiers in Cell and DevelopmentalBiology, 9(716462), 1–17. https://doi.org/10.3389/fcell.2021.716462

  11. Beatty, G. L. & Paterson, Y. (2001). IFN-γ-dependent inhibitionof tumor angiogenesis by tumor-infiltrating CD4 + T cellsrequires tumor responsiveness to IFN-γ . The Journal ofImmunology, 166(4), 2276–2282. https://doi.org/10.4049/jimmunol.166.4.2276

  12. Benci, J. L., Xu, B., Qiu, Y., Wu, T. J., Dada, H., Twyman-SaintVictor, C., Cucolo, L., Lee, D. S. M., Pauken, K. E., Huang,A. C., Gangadhar, T. C., Amaravadi, R. K., Schuchter, L. M.,Feldman, M. D., Ishwaran, H., Vonderheide, R. H., Maity,A., Wherry, E. J. & Minn, A. J. (2016). Tumor InterferonSignaling Regulates a Multigenic Resistance Program toImmune Checkpoint Blockade. Cell, 167(6), 1540-1554.e12. https://doi.org/10.1016/j.cell.2016.11.022

  13. Burke, J. D. & Young, H. A. (2019). IFN-γ: A cytokine at the righttime, is in the right place. Seminars in Immunology, 43(12),101280. https://doi.org/10.1016/j.smim.2019.05.002

  14. Chen, H. C., Chou, A. S. Bin, Liu, Y. C., Hsieh, C. H., Kang,C. C., Pang, S. T., Yeh, C. T., Liu, H. P. & Liao, S. K.(2011). Induction of metastatic cancer stem cells fromthe NK/LAK-resistant floating, but not adherent, subsetof the UP-LN1 carcinoma cell line by IFN-γ. LaboratoryInvestigation, 91(10), 1502–1513. https://doi.org/10.1038/labinvest.2011.91

  15. Chen, R. Q., Liu, F., Qiu, X. Y. & Chen, X. Q. (2019). Theprognostic and therapeutic value of PD-L1 in glioma.Frontiers in Pharmacology, 9(1503). https://doi.org/10.3389/fphar.2018.01503

  16. Chen, Z., Zhang, Y., Guan, Q., Zhang, H., Luo, J., Li, J., Wei,W., Xu, X., Liao, L., Wong, J. & Li, J. (2021). Linkingnuclear matrix–localized PIAS1 to chromatin SUMOylationvia direct binding of histones H3 and H2A.Z. Journalof Biological Chemistry, 279(4), 101200. https://doi.org/10.1016/j.jbc.2021.101200

  17. Chin, Y. E., Kitagawa, M., Su, W.-C. S., You, Z.-H., Iwamoto,Y. & Fu, X.-Y. (1996). Cell growth arrest and inductionof cyclin-dependent kinase inhibitor p21 WAF1/CIP1Mediated by STAT1. Science, 272(5262), 719–722. https://doi.org/10.1126/science.272.5262.719

  18. Cho, H. & Kelsall, B. L. (2014). The role of type I interferonsin intestinal infection, homeostasis and inflammation.Immunol Rev., 260(1), 145–167.

  19. Christie, S. M., Ham, T. R., Gilmore, G. T., Toth, P. D., Leipzig,N. D., Leipzig, N. D. & Smith, A. W. (2020). Covalentlyimmobilizing interferon-γ drives filopodia productionthrough specific receptor-ligand interactions independentlyof canonical downstream signaling. BioconjugateChemistry, 31(5), 1362–1369. https://doi.org/10.1021/acs.bioconjchem.0c00105

  20. Darnell, J. E., Kerr, I. M. & Stark, G. R. (1994). Jak-STATpathways and transcriptional activation in response to ifnsand other extracellular signaling proteins. Advancement OfScience, 264(5164), 1415–1421.

  21. Debrincat, M. A., Zhang, J. G., Willson, T. A., Silke, J., Connolly,L. M., Simpson, R. J., Alexander, W. S., Nicola, N. A.,Kile, B. T. & Hilton, D. J. (2007). Ankyrin repeat andsuppressors of cytokine signaling box protein Asb-9 targetscreatine kinase B for degradation. Journal of BiologicalChemistry, 282(7), 4728–4737. https://doi.org/10.1074/jbc.M609164200

  22. Du, W., Frankel, T. L., Green, M. & Zou, W. (2022). IFNγsignaling integrity in colorectal cancer immunity andimmunotherapy. Cellular and Molecular Immunology,19(1), 23–32. https://doi.org/10.1038/s41423-021-00735-3

  23. Ellis, T. N. & Beaman, B. L. (2004). Interferon-gammaactivation of polymorphonuclear neutrophil function.Immunology, 112(1), 2–12. https://doi.org/10.1111/j.1365-2567.2004.01849.x

  24. Eslam, M. & George, J. (2016). Targeting IFN-λ: therapeuticimplications. Expert Opinion on Therapeutic Targets,20(12), 1425–1432. https://doi.org/10.1080/14728222.2016.1241242

  25. Gao, J., Shi, L. Z., Zhao, H., Chen, J., Xiong, L., He, Q.,Chen, T., Roszik, J., Bernatchez, C., Woodman, S. E.,Chen, P. L., Hwu, P., Allison, J. P., Futreal, A., Wargo, J.A. & Sharma, P. (2016). Loss of IFN-γ pathway genes intumor cells as a mechanism of resistance to anti-CTLA-4therapy. Cell, 167(2), 397-404.e9. https://doi.org/10.1016/j.cell.2016.08.069

  26. Gerber, S. A., Sedlacek, A. L., Cron, K. R., Murphy, S. P.,Frelinger, J. G. & Lord, E. M. (2013). IFN-γ mediates theantitumor effects of radiation therapy in a murine colontumor. American Journal of Pathology, 182(6), 2345–2354.https://doi.org/10.1016/j.ajpath.2013.02.041

  27. Gocher, A. M., Workman, C. J. & Vignali, D. A. A. (2022).Interferon-γ: teammate or opponent in the tumourmicroenvironment? Nature Reviews Immunology, 22(3),158–172. https://doi.org/10.1038/s41577-021-00566-3

  28. Haan, C., Is’Harc, H., Hermanns, H. M., Schmitz-Van de Leur,H., Kerr, I. M., Heinrich, P. C., Grötzinger, J. & Behrmann,I. (2001). Mapping of a Region within the N Terminus ofJak1 Involved in Cytokine Receptor Interaction. Journalof Biological Chemistry, 276(40), 37451–37458. https://doi.org/10.1074/jbc.M106135200

  29. Hao, C., Chen, G., Zhao, H., Li, Y., Chen, J., Zhang, H., Li, S.,Zhao, Y., Chen, F., Li, W. & Jiang, W. G. (2020). PD-L1expression in glioblastoma, the clinical and prognosticsignificance: A systematic literature review and metaanalysis.Frontiers in Oncology, 10(June), 1–10. https://doi.org/10.3389/fonc.2020.01015

  30. Hernández-Romero, I. A., Guerra-Calderas, L., Salgado-Albarrán, M., Maldonado-Huerta, T. & Soto-Reyes,E. (2019). The regulatory roles of non-coding rnas inangiogenesis and neovascularization from an epigeneticperspective. Frontiers in Oncology, 9(Oct), 1–15. https://doi.org/10.3389/fonc.2019.01091

  31. Imai, Y., Chiba, T., Kondo, T., Kanzaki, H., Kanayama, K.,Ao, J., Kojima, R., Kusakabe, Y., Nakamura, M., Saito,T., Nakagawa, R., Suzuki, E., Nakamoto, S., Muroyama,R., Tawada, A., Matsumura, T., Nakagawa, T., Kato, J.,Kotani, A., Matsubara, H. & Kato, N. (2020). Interferon-γinduced PD-L1 expression and soluble PD-L1 productionin gastric cancer. Oncology Letters, 20(3), 2161–2168.https://doi.org/10.3892/ol.2020.11757

  32. Isaacs, A. & Lindenmann, J. (1957). Virus interference . I . Theinterferon. J. Proc. R. Soc. Lond., 12; 147(927), 258-267.

  33. Jiang, X., Wang, J., Deng, X., Xiong, F., Ge, J., Xiang, B., Wu,X., Ma, J., Zhou, M., Li, X., Li, Y., Li, G., Xiong, W., Guo,C. & Zeng, Z. (2019). Role of the tumor microenvironmentin PD-L1/PD-1-mediated tumor immune escape. MolecularCancer, 18(1), 1–18. https://doi.org/10.1186/s12943-018-0928-4

  34. Jorgovanovic, D., Song, M., Wang, L. & Zhang, Y. (2020). Rolesof IFN-γ in tumor progression and regression: a review.Biomarker Research, 8(1), 49.

  35. Jung, M.-Y., Aibaidula, A., Brown, D. A., Himes, B. T., CumbaGarcia, L. M. & Parney, I. F. (2022). Superinduction ofimmunosuppressive glioblastoma extracellular vesiclesby IFN-γ through PD-L1 and IDO1. Neuro-OncologyAdvances, 1–10. https://doi.org/10.1093/noajnl/vdac017

  36. Karachaliou, N., Gonzalez-Cao, M., Crespo, G., Drozdowskyj,A., Aldeguer, E., Gimenez-Capitan, A., Teixido, C.,Molina-Vila, M. A., Viteri, S., Gil, M. D. L. L., Algarra,S. M., Perez-Ruiz, E., Marquez-Rodas, I., Rodriguez-Abreu, D., Blanco, R., Puertolas, T., Royo, M. A. &Rosell, R. (2018). Interferon gamma, an importantmarker of response to immune checkpoint blockadein non-small cell lung cancer and melanoma patients.Therapeutic Advances in Medical Oncology, 10. https://doi.org/10.1177/1758834017749748

  37. Kim, Y. M. & Shin, E. C. (2021). Type I and III interferonresponses in SARS-CoV-2 infection. Experimental andMolecular Medicine, 53(5), 750–760.

  38. Kolli, S., Zito, C. I., Mossink, M. H., Wiemer, E. A. C. &Bennett, A. M. (2004). The major vault protein is a novelsubstrate for the tyrosine phosphatase SHP-2 and scaffoldprotein in epidermal growth factor signaling. Journal ofBiological Chemistry, 279(28), 29374–29385. https://doi.org/10.1074/jbc.M313955200

  39. Korentzelos, D., Wells, A. & Clark, A. M. (2022). Interferon-γincreases sensitivity to chemotherapy and providesimmunotherapy targets in models of metastatic castrationresistantprostate cancer. Scientific Reports, 12(1), 1–9.https://doi.org/10.1038/s41598-022-10724-9

  40. Krause, C. D., Lavnikova, N., Xie, J., Mei, E., Mirochnitchenko,O. V., Jia, Y., Hochstrasser, R. M. & Pestka, S. (2006).Preassembly and ligand-induced restructuring of the chainsof the IFN-γ receptor complex: The roles of Jak kinases,Stat1 and the receptor chains. Cell Research, 16(1), 55–69.https://doi.org/10.1038/sj.cr.7310008

  41. Krause, C. D., Mei, E., Xie, J., Jia, Y., Bopp, M. A., Hochstrasser,R. M. & Pestka, S. (2002). Seeing the light: preassembly andligand-induced changes of the interferon gamma receptorcomplex in cells. Molecular & Cellular Proteomics: MCP,1(10), 805–815. https://doi.org/10.1074/mcp.M200065-MCP200

  42. Kursunel, M. A. & Esendagli, G. (2016). The untold story of IFN-γin cancer biology. Cytokine and Growth Factor Reviews,31, 73–81. https://doi.org/10.1016/j.cytogfr.2016.07.005

  43. Lazear, H. M., Schoggins, J. W. & Diamond, M. S. (2019).Shared and Distinct Functions of Type I and Type IIIInterferons. Immunity, 50(4), 907–923.

  44. Lei, Q., Wang, D., Sun, K., Wang, L. & Zhang, Y. (2020).Resistance Mechanisms of Anti-PD1/PDL1 Therapy inSolid Tumors. Frontiers in Cell and Developmental Biology,8(July). https://doi.org/10.3389/fcell.2020.00672

  45. Liao, J., Fu, Y. & Shuai, K. (2000). Distinct roles of the NH2- andCOOH-terminal domains of the protein inhibitor of activatedsignal transducer and activator of transcription (STAT)1 (PIAS1) in cytokine-induced PIAS1-Stat1 interaction.Proceedings of the National Academy of Sciences of theUnited States of America, 97(10), 5267–5272. https://doi.org/10.1073/pnas.97.10.5267

  46. Liau, N. P. D., Laktyushin, A., Lucet, I. S., Murphy, J. M., Yao,S., Whitlock, E., Callaghan, K., Nicola, N. A., Kershaw, N.J. & Babon, J. J. (2018). The molecular basis of JAK/STATinhibition by SOCS1. Nature Communications, 9(1), 1–14.https://doi.org/10.1038/s41467-018-04013-1

  47. Litak, J., Mazurek, M., Grochowski, C., Kamieniak, P. &Roliński, J. (2019). PD-L1/PD-1 Axis in GlioblastomaMultiforme. International Journal of Molecular Sciences,20(21), 5347. https://doi.org/10.3390/ijms20215347

  48. Lo, U. G., Pong, R. C., Yang, D., Gandee, L., Dang, A., Lin, C.J., Santoyo, J., Hong, S., Sonavane, R., Huang, J., Tseng, S.F., Moro, L., Arbini, A. A., Kapur, P., Raj, G., He, D., Lai,C., Lin, H. & Hsieh, J. T. (2018). IFN-γ induces epithelialto-mesenchymal transition of cancer cells via an uniquemicroRNA processing. BioRxiv, 1–60.

  49. Lou, Y., Shi, J., Guo, D., Qureshi, A. K. & Song, L. (2017).Function of PD-L1 in antitumor immunity of glioma cells.Saudi Journal of Biological Sciences, 24(4), 803–807.https://doi.org/10.1016/j.sjbs.2015.06.025

  50. Lugade, A. A., Moran, J. P., Gerber, S. A., Rose, R. C., Frelinger,J. G. & Lord, E. M. (2005). Local Radiation Therapy ofB16 Melanoma Tumors Increases the Generation of TumorAntigen-Specific Effector Cells That Traffic to the Tumor.The Journal of Immunology, 174(12), 7516–7523. https://doi.org/10.4049/jimmunol.174.12.7516

  51. Mao, X., Ren, Z., Parker, G. N., Sondermann, H., Pastorello,M. A., Wang, W., McMurray, J. S., Demeler, B.,Darnell, J. E. & Chen, X. (2005). Structural bases ofunphosphorylated STAT1 association and receptor binding.Molecular Cell, 17(6), 761–771. https://doi.org/10.1016/j.molcel.2005.02.021

  52. Marsters, S. A., Pennica, D., Bach, E., Schreiber, R. D. &Ashkenazi, A. (1995). Interferon γ signals via a high-affinitymultisubunit receptor complex that contains two types ofpolypeptide chain. Proceedings of the National Academyof Sciences of the United States of America, 92(12), 5401–5405. https://doi.org/10.1073/pnas.92.12.5401

  53. Martin-Hijano, L. & Sainz, B. (2020). The Interactions BetweenCancer Stem Cells and the Innate Interferon SignalingPathway. Frontiers in Immunology, 11(March), 1–15.https://doi.org/10.3389/fimmu.2020.00526

  54. Mauldin, I. S., Wages, N. A., Stowman, A. M., Wang, E.,Smolkin, M. E., Olson, W. C., Deacon, D. H., Smith, K.T., Galeassi, N. V., Chianese-Bullock, K. A., Dengel, L.T., Marincola, F. M., Petroni, G. R., Mullins, D. W. &Slingluff, C. L. (2016). Intratumoral interferon-gammaincreases chemokine production but fails to increase Tcell infiltration of human melanoma metastases. CancerImmunology, Immunotherapy, 65(10), 1189–1199. https://doi.org/10.1007/s00262-016-1881-y

  55. Mimura, K., Teh, J. L., Okayama, H., Shiraishi, K., Kua, L.F., Koh, V., Smoot, D. T., Ashktorab, H., Oike, T., Suzuki,Y., Fazreen, Z., Asuncion, B. R., Shabbir, A., Yong, W. P.,So, J., Soong, R. & Kono, K. (2018). PD-L1 expressionis mainly regulated by interferon gamma associated withJAK-STAT pathway in gastric cancer. Cancer Science,109(1), 43–53. https://doi.org/10.1111/cas.13424

  56. Mondal, A., Smith, C., DuHadaway, J. B., Sutanto-Ward,E., Prendergast, G. C., Bravo-Nuevo, A. & Muller, A. J.(2016). IDO1 is an Integral Mediator of InflammatoryNeovascularization. EBioMedicine, 14, 74–82. https://doi.org/10.1016/j.ebiom.2016.11.013

  57. Okada, S., Ishikawa, N., Shirao, K., Kawaguchi, H., Tsumura,M., Ohno, Y., Yasunaga, S., Ohtsubo, M., Takihara, Y.& Kobayashi, M. (2007). The novel IFNGR1 mutation774del4 produces a truncated form of interferon-γ receptor1 and has a dominant-negative effect on interferon-γ signaltransduction. Journal of Medical Genetics, 44(8), 485–491.https://doi.org/10.1136/jmg.2007.049635

  58. Owen, K. L., Brockwell, N. K. & Parker, B. S. (2019). JAK-STATSignaling: A Double-Edged Sword of Immune Regulationand Cancer Progression. Cancers, 11(12), 2002. https://doi.org/10.3390/cancers11122002

  59. Patel, S. J., Sanjana, N. E., Kishton, R. J., Eidizadeh, A., Vodnala,S. K., Cam, M., Gartner, J. J., Jia, L., Steinberg, S. M.,Yamamoto, T. N., Merchant, A. S., Mehta, G. U., Chichura,A., Shalem, O., Tran, E., Eil, R., Sukumar, M., Guijarro,E. P., Day, C. P., … Restifo, N. P. (2017). Identificationof essential genes for cancer immunotherapy. Nature,548(7669), 537–542. https://doi.org/10.1038/nature23477

  60. Pearson, J. R. D., Cuzzubbo, S., McArthur, S., Durrant, L. G.,Adhikaree, J., Tinsley, C. J., Pockley, A. G. & McArdle, S. E.B. (2020). Immune Escape in Glioblastoma Multiforme andthe Adaptation of Immunotherapies for Treatment. Frontiersin Immunology, 11(October). https://doi.org/10.3389/fimmu.2020.582106

  61. Rettino, A. & Nicole, M. C. (2013). Genome-wide Identificationof IRF1 Binding Sites Reveals Extensive Occupancy atCell Death Associated Genes. Journal of Carcinogenesis& Mutagenesis, 44(0). https://doi.org/10.4172/2157-2518.S6-009

  62. Schindler, C., Levy, D. E. & Decker, T. (2007). JAK-STATsignaling: From interferons to cytokines. Journal ofBiological Chemistry, 282(28), 20059–20063. https://doi.org/10.1074/jbc.R700016200

  63. Schroder, K., Hertzog, P. J., Ravasi, T. & Hume, D. A. (2004).Interferon-γ: an overview of signals, mechanisms andfunctions. Journal of Leukocyte Biology, 75(2), 163–189.https://doi.org/10.1189/jlb.0603252

  64. Shao, L., Hou, W., Scharping, N. E., Vendetti, F. P., Srivastava,R., Roy, C. N., Menk, A. V, Wang, Y., Chauvin, J.,Karukonda, P., Thorne, S. H., Hornung, V., Zarour, H.M., Bakkenist, C. J., Delgoffe, G. M. & Sarkar, S. N.(2019). IRF1 Inhibits Antitumor Immunity throughthe Upregulation of PD-L1 in the Tumor Cell. CancerImmunology Research, 7(8), 1258–1266. https://doi.org/10.1158/2326-6066.CIR-18-0711

  65. Song, M., Ping, Y., Zhang, K., Yang, L., Li, F., Zhang, C., Cheng,S., Yue, D., Maimela, N. R., Qu, J., Liu, S., Sun, T., Li, Z., Xia,J., Zhang, B., Wang, L. & Zhang, Y. (2019). Low-dose IFNginduces tumor cell stemness in tumor microenvironmentof non–small cell lung cancer. Cancer Research, 79(14),3737–3748. https://doi.org/10.1158/0008-5472.CAN-19-0596

  66. Sun, C., Mezzadra, R. & Schumacher, T. N. (2018). Regulationand Function of the PD-L1 Checkpoint. Immunity, 48(3),434–452. https://doi.org/10.1016/j.immuni.2018.03.014.Regulation

  67. Torrisi, F., Alberghina, C., D’Aprile, S., Pavone, A. M.,Longhitano, L., Giallongo, S., Tibullo, D., Di Rosa, M.,Zappalà, A., Cammarata, F. P., Russo, G., Ippolito, M.,Cuttone, G., Li Volti, G., Vicario, N. & Parenti, R. (2022).The Hallmarks of Glioblastoma: Heterogeneity, IntercellularCrosstalk and Molecular Signature of Invasivenessand Progression. Biomedicines, 10(4), 806. https://doi.org/10.3390/biomedicines10040806

  68. Tseng, P. C., Huang, W. C., Chen, C. L., Sheu, B. S., Shan, Y.S., Tsai, C. C., Wang, C. Y., Chen, S. O., Hsieh, C. Y. & Lin,C. F. (2012). Regulation of SHP2 by PTEN/AKT/GSK-3βsignaling facilitates IFN-γ resistance in hyperproliferatinggastric cancer. Immunobiology, 217(9), 926–934. https://doi.org/10.1016/j.imbio.2012.01.001

  69. Uniprot. (1989). IRF1 - Human. UniProtKB/Swiss-Prot. https://www.uniprot.org/uniprot/P10914

  70. Uniprot. (1991). JAK1 - Human. UniProtKB/Swiss-Prot. https://www.uniprot.org/uniprot/P23458

  71. Uniprot. (1994a). IFNGR2 - Human. UniProtKB/Swiss-Prot.https://www.uniprot.org/uniprot/P38484

  72. Uniprot. (1994b). PTN11 - Human. UniProtKB/Swiss-Prot.https://www.uniprot.org/uniprot/Q06124

  73. Uniprot. (1995). STAT1 - Human. UniProtKB/Swiss-Prot.https://www.uniprot.org/uniprot/P42224

  74. Uniprot. (1998). JAK2 - Human. UniProtKB/Swiss-Prot. https://www.uniprot.org/uniprot/O60674

  75. Uniprot. (2002a). PIAS1 - Human. UniProtKB/Swiss-Prot.https://www.uniprot.org/uniprot/O7592580. Uniprot. (2002b). SOCS1-Human. UniProtKB/Swiss-Prot.https://www.uniprot.org/uniprot/O1552481. Uniprot. (2005). PD1L1 - Human. UniProtKB/Swiss-Prot.https://www.uniprot.org/uniprot/Q9NZQ7

  76. van de Vosse, E. & van Dissel, J. T. (2017). IFN-γR1 defects:Mutation update and description of the IFNGR1 variationdatabase. Human Mutation, 38(10), 1286–1296. https://doi.org/10.1002/humu.23302

  77. Wang, R., Bao, W., Pal, M., Liu, Y., Yazdanbakhsh, K. &Zhong, H. (2022). Intermediate monocytes induced byIFN-γ inhibit cancer metastasis by promoting NK cellactivation through FOXO1 and interleukin-27. Journalfor ImmunoTherapy of Cancer, 10(1), 1–12. https://doi.org/10.1136/jitc-2021-003539

  78. Wen, Z., Zhong, Z. & Darnell, J. E. (1995). Maximal activationof transcription by statl and stat3 requires both tyrosine andserine phosphorylation. Cell, 82(2), 241–250. https://doi.org/10.1016/0092-8674(95)90311-9

  79. Wilks, A. F., Harpur, A. G., Kurban, R. R., Ralph, S. J., Zürcher,G. & Ziemiecki, A. (1991). Two novel protein-tyrosinekinases, each with a second phosphotransferase-relatedcatalytic domain, define a new class of protein kinase.Molecular and Cellular Biology, 11(4), 2057–2065. https://doi.org/10.1128/mcb.11.4.2057

  80. Xu, D. & Qu, C.-K. (2008). Protein tyrosine phosphatases inthe JAK/STAT pathway. Frontiers in Bioscience, Volume(13), 4925. https://doi.org/10.2741/3051

  81. Yamashita, T., Uchida, T., Araki, A. & Sendo, F. (1997).Nitric oxide is an effector molecule in inhibition oftumor cell growth by rIFN-γ-activated rat neutrophils.International Journal of Cancer, 71(2), 223–230. https://doi.org/10.1002/(SICI)1097-0215(19970410)71:2<223::AIDIJC17>3.0.CO;2-I

  82. Yan, K., Lu, Y., Yan, Z. & Wang, Y. (2021). 9-Gene SignatureCorrelated With CD8+ T Cell Infiltration Activated by IFN-γ:A Biomarker of Immune Checkpoint Therapy Response inMelanoma. Frontiers in Immunology, 12(622563), 1–15.https://doi.org/10.3389/fimmu.2021.622563

  83. Zaidi, M. R. (2019). The Interferon-Gamma Paradox in Cancer.Journal of Interferon & Cytokine Research, 39(1), 30–38.https://doi.org/10.1089/jir.2018.0087

  84. Zhou, Y., Weyman, C. M., Liu, H., Almassan, A. & Zhou, A.(2008). IFN-γ induces apoptosis in HL-60 cells throughdecreased Bcl-2 and increased Bak expression. Journal ofInterferon and Cytokine Research, 28(2), 65–72. https://doi.org/10.1089/jir.2007.0025




2020     |     www.medigraphic.com