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Published in: Journal of Cancer Research and Clinical Oncology 10/2008

01-10-2008 | Original Paper

Suppression of FasL expression in tumor cells and preventing TNF-induced apoptosis was better for immune cells survival

Authors: Gaosi Xu, Jiangguo Zhang

Published in: Journal of Cancer Research and Clinical Oncology | Issue 10/2008

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Abstract

Objective

To elucidate if Fas/FasL signal pathway participates in the immune escape of tumor cells, and if contemporarily preventing Fas/FasL and TNF-induced apoptosis is better for immune cells survival than just blocking Fas/FasL-induced apoptotic signal.

Methods

Suppression of FasL expression in mouse H22 hepatocellular cancer cells by siRNA technique. Wild-type Ad5 14.7K gene was amplified by PCR and transduced into Jurkat T cells. Detecting apoptosis of target Jurkat cells by Flow Cytometry. Detection of TNF-α in the culture supernatant of H22 cells by ELISA. FasL and 14.7K gene expression in stably transfected or transduced clones were determined by western blotting.

Results

FasL expression in H22 cells was down-regulated following stable transfection with a plasmid encoding antisense FasL cDNA. Down-regulation of FasL expression in H22 cells had no effect on tumor growth in vitro. There was an apparent decrease in the number of apoptotic Jurkat T cells following coculture with transfected H22 cells, relative to coculture with FasL-expressing untransfected cells. Compared with untransduced Jurkat cells, apoptotic rates in 14.7K transduced Jurkat cells were significantly reduced in three different E/T ratios (P < 0.01), respectively.

Conclusions

Fas/FasL signal pathway participated in the immune escape of tumor cells by inducing immune cells apoptosis. Reducing the expression of FasL in tumor cells can decrease the apoptotic rate of immune cells. Further blocking of apoptotic signal pathway of immune cells by preventing TNF-induced apoptosis can increase the survival of immune cells.
Literature
go back to reference Ahmad M, Rees RC, Ali SA (2004) Escape from immunotherapy: possible mechanisms that influence tumor regression/progression. Cancer Immunol Immunother 53:844–854PubMedCrossRef Ahmad M, Rees RC, Ali SA (2004) Escape from immunotherapy: possible mechanisms that influence tumor regression/progression. Cancer Immunol Immunother 53:844–854PubMedCrossRef
go back to reference Arai H, Chan SY, Bishop DK et al (1997) Inhibition of the alloantibody response by CD95 ligand. Nat Med 3:843–848PubMedCrossRef Arai H, Chan SY, Bishop DK et al (1997) Inhibition of the alloantibody response by CD95 ligand. Nat Med 3:843–848PubMedCrossRef
go back to reference Aubry JP, Blaecke A, Lecoanet-Henchoz S et al (1999) Annexin V used for measuring apoptosis in the early events of cellular cytotoxicity. Cytometry 37:197–204PubMedCrossRef Aubry JP, Blaecke A, Lecoanet-Henchoz S et al (1999) Annexin V used for measuring apoptosis in the early events of cellular cytotoxicity. Cytometry 37:197–204PubMedCrossRef
go back to reference Cefai D, Favre L, Wattendorf E et al (2001a) Role of Fas ligand expression in promoting escape from immune rejection in a spontaneous tumor model. Int J Cancer 91:529–537PubMedCrossRef Cefai D, Favre L, Wattendorf E et al (2001a) Role of Fas ligand expression in promoting escape from immune rejection in a spontaneous tumor model. Int J Cancer 91:529–537PubMedCrossRef
go back to reference Cefai D, Schwaninger R, Balli M et al (2001b) Functional characterization of Fas ligand on tumor cells escaping active specific immunotherapy. Cell Death Differ 8:687–695PubMedCrossRef Cefai D, Schwaninger R, Balli M et al (2001b) Functional characterization of Fas ligand on tumor cells escaping active specific immunotherapy. Cell Death Differ 8:687–695PubMedCrossRef
go back to reference Chen P, Tian J, Kovesdi I et al (1998) Interaction of the adenovirus 14.7-kDa protein with FLICE inhibits Fas ligand-induced apoptosis. J Biol Chem 273:5815–5820PubMedCrossRef Chen P, Tian J, Kovesdi I et al (1998) Interaction of the adenovirus 14.7-kDa protein with FLICE inhibits Fas ligand-induced apoptosis. J Biol Chem 273:5815–5820PubMedCrossRef
go back to reference Chinnadurai G. (1998) Control of apoptosis by human adenovirus genes. Semin Virol 8:399–408CrossRef Chinnadurai G. (1998) Control of apoptosis by human adenovirus genes. Semin Virol 8:399–408CrossRef
go back to reference Clarke P, Meintzer S, Gibson S et al (2000) Reovirus-induced apoptosis is mediated by TRAIL. J Virol 74:8135–8139PubMedCrossRef Clarke P, Meintzer S, Gibson S et al (2000) Reovirus-induced apoptosis is mediated by TRAIL. J Virol 74:8135–8139PubMedCrossRef
go back to reference Elsing A, Burgert HG (1998) The adenovirus E3/10.4K–14.5K proteins down-modulate the apoptosis receptor Fas/Apo-1 by inducing its internalization. Proc Natl Acad Sci USA 95:10072–10077PubMedCrossRef Elsing A, Burgert HG (1998) The adenovirus E3/10.4K–14.5K proteins down-modulate the apoptosis receptor Fas/Apo-1 by inducing its internalization. Proc Natl Acad Sci USA 95:10072–10077PubMedCrossRef
go back to reference Falcone M, Sarvetnick N (1999) Cytokines that regulate autoimmune responses. Curr Opin Immunol 11:670–676PubMedCrossRef Falcone M, Sarvetnick N (1999) Cytokines that regulate autoimmune responses. Curr Opin Immunol 11:670–676PubMedCrossRef
go back to reference Fanger N, Maliszewski C, Schooley K et al (1999) Human dendritic cells mediate cellular apoptosis via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). J Exp Med 190:1155–1164PubMedCrossRef Fanger N, Maliszewski C, Schooley K et al (1999) Human dendritic cells mediate cellular apoptosis via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). J Exp Med 190:1155–1164PubMedCrossRef
go back to reference Ferguson TA, Green DR (2001) Fas ligand and immune privilege: the eyes have it. Cell Death Differ 8:771–772PubMedCrossRef Ferguson TA, Green DR (2001) Fas ligand and immune privilege: the eyes have it. Cell Death Differ 8:771–772PubMedCrossRef
go back to reference Flavio SO, Mercedes NL, Ariadna MN (2007) Paradoxical effects of cytokines in tumor immune surveillance and tumor immune escape. Cytokine Growth Factor Rev 18:171–182CrossRef Flavio SO, Mercedes NL, Ariadna MN (2007) Paradoxical effects of cytokines in tumor immune surveillance and tumor immune escape. Cytokine Growth Factor Rev 18:171–182CrossRef
go back to reference Gooding LR, Elmore LW, Tollefson AE et al (1988) A 14, 700 MW protein from the E3 region of adenovirus inhibits cytolysis by tumor necrosis factor. Cell 53:341–346PubMedCrossRef Gooding LR, Elmore LW, Tollefson AE et al (1988) A 14, 700 MW protein from the E3 region of adenovirus inhibits cytolysis by tumor necrosis factor. Cell 53:341–346PubMedCrossRef
go back to reference Gooding LR, Sofola IO, Tollefson AE et al (1990) The adenovirus E3–14.7K protein is a general inhibitor of tumor necrosis factor-mediated cytolysis. J Immunol 145:3080–3086PubMed Gooding LR, Sofola IO, Tollefson AE et al (1990) The adenovirus E3–14.7K protein is a general inhibitor of tumor necrosis factor-mediated cytolysis. J Immunol 145:3080–3086PubMed
go back to reference Griffith TS, Wiley SR, Kubin M et al (1999) Monocyte-mediated tumoricidal activity via the tumor necrosis factor-related cytokine, TRAIL. J Exp Med 189:1343–1353PubMedCrossRef Griffith TS, Wiley SR, Kubin M et al (1999) Monocyte-mediated tumoricidal activity via the tumor necrosis factor-related cytokine, TRAIL. J Exp Med 189:1343–1353PubMedCrossRef
go back to reference Horton TM, Ranheim TS, Aquino L et al (1991) Adenovirus E3 14.7K protein functions in the absence of other adenovirus proteins to protect transfected cells from tumor necrosis factor cytolysis. J Virol 65:2629–2639PubMed Horton TM, Ranheim TS, Aquino L et al (1991) Adenovirus E3 14.7K protein functions in the absence of other adenovirus proteins to protect transfected cells from tumor necrosis factor cytolysis. J Virol 65:2629–2639PubMed
go back to reference Jeremias I, Herr I, Boehler T et al (1998) TRAIL/Apo2-ligand-induced apoptosis in human T cells. Eur J Immunol 28:143–152PubMedCrossRef Jeremias I, Herr I, Boehler T et al (1998) TRAIL/Apo2-ligand-induced apoptosis in human T cells. Eur J Immunol 28:143–152PubMedCrossRef
go back to reference Khar A, Varalakshmi C, Pardhasaradhi BV et al (1998) Depletion of the natural killer cell population in the peritoneum by AK-5 tumor cells overexpressing fas-ligand: a mechanism of immune evasion. Cell Immunol 189:85–91PubMedCrossRef Khar A, Varalakshmi C, Pardhasaradhi BV et al (1998) Depletion of the natural killer cell population in the peritoneum by AK-5 tumor cells overexpressing fas-ligand: a mechanism of immune evasion. Cell Immunol 189:85–91PubMedCrossRef
go back to reference Niehans GA, Brunner T, Frizelle SP et al (1997) Human lung carcinomas express Fas ligand. Cancer Res 57:1007–1012PubMed Niehans GA, Brunner T, Frizelle SP et al (1997) Human lung carcinomas express Fas ligand. Cancer Res 57:1007–1012PubMed
go back to reference O’Connell J, O’Sullivan GC, Collins JK et al (1996) The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. J Exp Med 184:1075–1082PubMedCrossRef O’Connell J, O’Sullivan GC, Collins JK et al (1996) The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. J Exp Med 184:1075–1082PubMedCrossRef
go back to reference Schmid S, Hearing P (1999) Adenovirus DNA packaging. Construction and analysis of viral mutants. In: Wold WS (ed) Adenovirus methods and protocols. Humana Press, Totowa, pp 47–59 Schmid S, Hearing P (1999) Adenovirus DNA packaging. Construction and analysis of viral mutants. In: Wold WS (ed) Adenovirus methods and protocols. Humana Press, Totowa, pp 47–59
go back to reference Schneider-Brachert W, Tchikov V, Merkel O (2006) Inhibition of TNF receptor 1 internalization by adenovirus 14.7K as a novel immune escape mechanism. J Clin Invest 116:2901–2913PubMedCrossRef Schneider-Brachert W, Tchikov V, Merkel O (2006) Inhibition of TNF receptor 1 internalization by adenovirus 14.7K as a novel immune escape mechanism. J Clin Invest 116:2901–2913PubMedCrossRef
go back to reference Schulze-Osthoff K, Ferrari D, Los M et al (1998) Apoptosis signaling by death receptors. Eur J Biochem 254:439–459PubMedCrossRef Schulze-Osthoff K, Ferrari D, Los M et al (1998) Apoptosis signaling by death receptors. Eur J Biochem 254:439–459PubMedCrossRef
go back to reference Song E, Chen J, Ouyang N et al (2001) Soluble Fas ligand released by colon adenocarcinoma cells induces host lymphocyte apoptosis: an active mode of immune evasion in colon cancer. Br J Cancer 85:1047–1054PubMedCrossRef Song E, Chen J, Ouyang N et al (2001) Soluble Fas ligand released by colon adenocarcinoma cells induces host lymphocyte apoptosis: an active mode of immune evasion in colon cancer. Br J Cancer 85:1047–1054PubMedCrossRef
go back to reference Teodoro JG, Branton PE (1997) Regulation of apoptosis by viral gene products. J Virol 71:1739–1746PubMed Teodoro JG, Branton PE (1997) Regulation of apoptosis by viral gene products. J Virol 71:1739–1746PubMed
go back to reference Tollefson AE, Hermiston TW, Lichtenstein DL et al (1998) Forced degradation of Fas inhibits apoptosis in adenovirus-infected cells. Nature 392:726–730PubMedCrossRef Tollefson AE, Hermiston TW, Lichtenstein DL et al (1998) Forced degradation of Fas inhibits apoptosis in adenovirus-infected cells. Nature 392:726–730PubMedCrossRef
go back to reference Vidalain P, Azocar O, Lamouille B et al (2000) Measles virus induces functional TRAIL production by human dendritic cells. J Virol 74:556–559PubMedCrossRef Vidalain P, Azocar O, Lamouille B et al (2000) Measles virus induces functional TRAIL production by human dendritic cells. J Virol 74:556–559PubMedCrossRef
go back to reference Walczak H, Miller RE, Ariail K et al (1999) Tumoricidal activity of tumor necrosis factor-related apoptosisinducing ligand in vivo. Nat Med 5:157–163PubMedCrossRef Walczak H, Miller RE, Ariail K et al (1999) Tumoricidal activity of tumor necrosis factor-related apoptosisinducing ligand in vivo. Nat Med 5:157–163PubMedCrossRef
go back to reference White E (1998) Regulation of apoptosis by adenovirus E1A and E1B oncogenes. Semin Virol 8:505–513CrossRef White E (1998) Regulation of apoptosis by adenovirus E1A and E1B oncogenes. Semin Virol 8:505–513CrossRef
go back to reference Windheim M, Hilgendorf A, Burgert HG (2004) Immune evasion by adenovirus E3 proteins: exploitation of intracellular trafficking pathways. Curr Top Microbiol Immunol 273:79–85 Windheim M, Hilgendorf A, Burgert HG (2004) Immune evasion by adenovirus E3 proteins: exploitation of intracellular trafficking pathways. Curr Top Microbiol Immunol 273:79–85
Metadata
Title
Suppression of FasL expression in tumor cells and preventing TNF-induced apoptosis was better for immune cells survival
Authors
Gaosi Xu
Jiangguo Zhang
Publication date
01-10-2008
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 10/2008
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-008-0393-3

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