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Erschienen in: Cancer Immunology, Immunotherapy 6/2016

31.03.2016 | Original Article

2′–5′ Oligoadenylate synthetase-like 1 (OASL1) deficiency in mice promotes an effective anti-tumor immune response by enhancing the production of type I interferons

verfasst von: Chan Kyu Sim, Yeon Sook Cho, Byung Soo Kim, In-Jeoung Baek, Young-Joon Kim, Myeong Sup Lee

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 6/2016

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Abstract

Type I interferon (IFN-I) plays a critical role in antiviral and antitumor defense. In our previous studies, we showed that IFN-I-inducible 2′–5′ oligoadenylate synthetase-like 1 (OASL1) negatively regulates IFN-I production upon viral infection by specifically inhibiting translation of the IFN-I-regulating master transcription factor, interferon regulatory factor 7 (IRF7). In this study, we investigated whether OASL1 plays a negative role in the anti-tumor immune response by using OASL1-deficient (Oasl1 /) mice and transplantable syngeneic tumor cell models. We found that Oasl1 / mice demonstrate enhanced resistance to lung metastatic tumors and subcutaneously implanted tumors compared to wild-type (WT) mice. Additionally, we found that cytotoxic effector cells such as CD8+ T cells (including tumor antigen-specific CD8+ T cells) and NK cells as well as CD8α+ DCs (the major antigen cross-presenting cells) were much more frequent (>fivefold) in the Oasl1 / mouse tumors. Furthermore, the cytotoxic effector cells in Oasl1 / mouse tumors seemed to be more functionally active. However, the proportion of immunosuppressive myeloid-derived suppressor cells within hematopoietic cells and of regulatory T cells within CD4+ T cells in Oasl1 / mouse tumors did not differ significantly from that of WT mice. Tumor-challenged Oasl1 / mice expressed increased levels of IFN-I and IRF7 protein in the growing tumor, indicating that the enhanced antitumor immune response observed in Oasl1 / mice was caused by higher IFN-I production in Oasl1 / mice. Collectively, these results show that OASL1 deficiency promotes the antitumor immune response, and thus, OASL1 could be a good therapeutic target for treating tumors.
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Literatur
1.
Zurück zum Zitat Urruticoechea A, Alemany R, Balart J, Villanueva A, Vinals F, Capella G (2010) Recent advances in cancer therapy: an overview. Curr Pharm Des 16(1):3–10CrossRefPubMed Urruticoechea A, Alemany R, Balart J, Villanueva A, Vinals F, Capella G (2010) Recent advances in cancer therapy: an overview. Curr Pharm Des 16(1):3–10CrossRefPubMed
8.
Zurück zum Zitat Diamond MS, Kinder M, Matsushita H, Mashayekhi M, Dunn GP, Archambault JM, Lee H, Arthur CD, White JM, Kalinke U, Murphy KM, Schreiber RD (2011) Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med 208(10):1989–2003. doi:10.1084/jem.20101158 CrossRefPubMedPubMedCentral Diamond MS, Kinder M, Matsushita H, Mashayekhi M, Dunn GP, Archambault JM, Lee H, Arthur CD, White JM, Kalinke U, Murphy KM, Schreiber RD (2011) Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med 208(10):1989–2003. doi:10.​1084/​jem.​20101158 CrossRefPubMedPubMedCentral
9.
10.
Zurück zum Zitat Poeck H, Besch R, Maihoefer C, Renn M, Tormo D, Morskaya SS, Kirschnek S, Gaffal E, Landsberg J, Hellmuth J, Schmidt A, Anz D, Bscheider M, Schwerd T, Berking C, Bourquin C, Kalinke U, Kremmer E, Kato H, Akira S, Meyers R, Hacker G, Neuenhahn M, Busch D, Ruland J, Rothenfusser S, Prinz M, Hornung V, Endres S, Tuting T, Hartmann G (2008) 5′-Triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma. Nat Med 14(11):1256–1263. doi:10.1038/nm.1887 CrossRefPubMed Poeck H, Besch R, Maihoefer C, Renn M, Tormo D, Morskaya SS, Kirschnek S, Gaffal E, Landsberg J, Hellmuth J, Schmidt A, Anz D, Bscheider M, Schwerd T, Berking C, Bourquin C, Kalinke U, Kremmer E, Kato H, Akira S, Meyers R, Hacker G, Neuenhahn M, Busch D, Ruland J, Rothenfusser S, Prinz M, Hornung V, Endres S, Tuting T, Hartmann G (2008) 5′-Triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma. Nat Med 14(11):1256–1263. doi:10.​1038/​nm.​1887 CrossRefPubMed
11.
Zurück zum Zitat Aranda F, Vacchelli E, Obrist F, Eggermont A, Galon J, Sautes-Fridman C, Cremer I, Henrik Ter Meulen J, Zitvogel L, Kroemer G, Galluzzi L (2014) Trial Watch: toll-like receptor agonists in oncological indications. Oncoimmunology 3:e29179. doi:10.4161/onci.29179 CrossRefPubMedPubMedCentral Aranda F, Vacchelli E, Obrist F, Eggermont A, Galon J, Sautes-Fridman C, Cremer I, Henrik Ter Meulen J, Zitvogel L, Kroemer G, Galluzzi L (2014) Trial Watch: toll-like receptor agonists in oncological indications. Oncoimmunology 3:e29179. doi:10.​4161/​onci.​29179 CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Deng L, Liang H, Xu M, Yang X, Burnette B, Arina A, Li XD, Mauceri H, Beckett M, Darga T, Huang X, Gajewski TF, Chen ZJ, Fu YX, Weichselbaum RR (2014) STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors. Immunity 41(5):843–852. doi:10.1016/j.immuni.2014.10.019 CrossRefPubMed Deng L, Liang H, Xu M, Yang X, Burnette B, Arina A, Li XD, Mauceri H, Beckett M, Darga T, Huang X, Gajewski TF, Chen ZJ, Fu YX, Weichselbaum RR (2014) STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors. Immunity 41(5):843–852. doi:10.​1016/​j.​immuni.​2014.​10.​019 CrossRefPubMed
14.
16.
18.
Zurück zum Zitat Ji H, Chang EY, Lin KY, Kurman RJ, Pardoll DM, Wu TC (1998) Antigen-specific immunotherapy for murine lung metastatic tumors expressing human papillomavirus type 16 E7 oncoprotein. International journal of cancer Journal international du cancer 78(1):41–45CrossRefPubMed Ji H, Chang EY, Lin KY, Kurman RJ, Pardoll DM, Wu TC (1998) Antigen-specific immunotherapy for murine lung metastatic tumors expressing human papillomavirus type 16 E7 oncoprotein. International journal of cancer Journal international du cancer 78(1):41–45CrossRefPubMed
21.
Zurück zum Zitat Schnorrer P, Behrens GM, Wilson NS, Pooley JL, Smith CM, El-Sukkari D, Davey G, Kupresanin F, Li M, Maraskovsky E, Belz GT, Carbone FR, Shortman K, Heath WR, Villadangos JA (2006) The dominant role of CD8 + dendritic cells in cross-presentation is not dictated by antigen capture. Proc Natl Acad Sci USA 103(28):10729–10734. doi:10.1073/pnas.0601956103 CrossRefPubMedPubMedCentral Schnorrer P, Behrens GM, Wilson NS, Pooley JL, Smith CM, El-Sukkari D, Davey G, Kupresanin F, Li M, Maraskovsky E, Belz GT, Carbone FR, Shortman K, Heath WR, Villadangos JA (2006) The dominant role of CD8 + dendritic cells in cross-presentation is not dictated by antigen capture. Proc Natl Acad Sci USA 103(28):10729–10734. doi:10.​1073/​pnas.​0601956103 CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Monjazeb AM, Tietze JK, Grossenbacher SK, Hsiao HH, Zamora AE, Mirsoian A, Koehn B, Blazar BR, Weiss JM, Wiltrout RH, Sckisel GD, Murphy WJ (2014) Bystander activation and anti-tumor effects of CD8 + T cells following Interleukin-2 based immunotherapy is independent of CD4 + T cell help. PLoS ONE 9(8):e102709. doi:10.1371/journal.pone.0102709 CrossRefPubMedPubMedCentral Monjazeb AM, Tietze JK, Grossenbacher SK, Hsiao HH, Zamora AE, Mirsoian A, Koehn B, Blazar BR, Weiss JM, Wiltrout RH, Sckisel GD, Murphy WJ (2014) Bystander activation and anti-tumor effects of CD8 + T cells following Interleukin-2 based immunotherapy is independent of CD4 + T cell help. PLoS ONE 9(8):e102709. doi:10.​1371/​journal.​pone.​0102709 CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Honda K, Ohba Y, Yanai H, Negishi H, Mizutani T, Takaoka A, Taya C, Taniguchi T (2005) Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction. Nature 434(7036):1035–1040. doi:10.1038/nature03547 CrossRefPubMed Honda K, Ohba Y, Yanai H, Negishi H, Mizutani T, Takaoka A, Taya C, Taniguchi T (2005) Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction. Nature 434(7036):1035–1040. doi:10.​1038/​nature03547 CrossRefPubMed
30.
Zurück zum Zitat Hervas-Stubbs S, Perez-Gracia JL, Rouzaut A, Sanmamed MF, Le Bon A, Melero I (2011) Direct effects of type I interferons on cells of the immune system. Clinical cancer research : an official journal of the American Association for Cancer Research 17(9):2619–2627. doi:10.1158/1078-0432.CCR-10-1114 CrossRef Hervas-Stubbs S, Perez-Gracia JL, Rouzaut A, Sanmamed MF, Le Bon A, Melero I (2011) Direct effects of type I interferons on cells of the immune system. Clinical cancer research : an official journal of the American Association for Cancer Research 17(9):2619–2627. doi:10.​1158/​1078-0432.​CCR-10-1114 CrossRef
32.
Zurück zum Zitat den Haan JM, Lehar SM, Bevan MJ (2000) CD8(+) but not CD8(-) dendritic cells cross-prime cytotoxic T cells in vivo. J Exp Med 192(12):1685–1696CrossRef den Haan JM, Lehar SM, Bevan MJ (2000) CD8(+) but not CD8(-) dendritic cells cross-prime cytotoxic T cells in vivo. J Exp Med 192(12):1685–1696CrossRef
34.
Zurück zum Zitat Crozat K, Tamoutounour S, Vu Manh TP, Fossum E, Luche H, Ardouin L, Guilliams M, Azukizawa H, Bogen B, Malissen B, Henri S, Dalod M (2011) Cutting edge: expression of XCR1 defines mouse lymphoid-tissue resident and migratory dendritic cells of the CD8alpha + type. Journal of immunology 187(9):4411–4415. doi:10.4049/jimmunol.1101717 CrossRef Crozat K, Tamoutounour S, Vu Manh TP, Fossum E, Luche H, Ardouin L, Guilliams M, Azukizawa H, Bogen B, Malissen B, Henri S, Dalod M (2011) Cutting edge: expression of XCR1 defines mouse lymphoid-tissue resident and migratory dendritic cells of the CD8alpha + type. Journal of immunology 187(9):4411–4415. doi:10.​4049/​jimmunol.​1101717 CrossRef
35.
Zurück zum Zitat Lorenzi S, Mattei F, Sistigu A, Bracci L, Spadaro F, Sanchez M, Spada M, Belardelli F, Gabriele L, Schiavoni G (2011) Type I IFNs control antigen retention and survival of CD8alpha(+) dendritic cells after uptake of tumor apoptotic cells leading to cross-priming. Journal of immunology 186(9):5142–5150. doi:10.4049/jimmunol.1004163 CrossRef Lorenzi S, Mattei F, Sistigu A, Bracci L, Spadaro F, Sanchez M, Spada M, Belardelli F, Gabriele L, Schiavoni G (2011) Type I IFNs control antigen retention and survival of CD8alpha(+) dendritic cells after uptake of tumor apoptotic cells leading to cross-priming. Journal of immunology 186(9):5142–5150. doi:10.​4049/​jimmunol.​1004163 CrossRef
36.
Zurück zum Zitat Curtsinger JM, Valenzuela JO, Agarwal P, Lins D, Mescher MF (2005) Type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation. Journal of immunology 174(8):4465–4469CrossRef Curtsinger JM, Valenzuela JO, Agarwal P, Lins D, Mescher MF (2005) Type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation. Journal of immunology 174(8):4465–4469CrossRef
38.
Zurück zum Zitat Havenar-Daughton C, Kolumam GA, Murali-Krishna K (2006) Cutting Edge: the direct action of type I IFN on CD4 T cells is critical for sustaining clonal expansion in response to a viral but not a bacterial infection. Journal of immunology 176(6):3315–3319CrossRef Havenar-Daughton C, Kolumam GA, Murali-Krishna K (2006) Cutting Edge: the direct action of type I IFN on CD4 T cells is critical for sustaining clonal expansion in response to a viral but not a bacterial infection. Journal of immunology 176(6):3315–3319CrossRef
40.
Zurück zum Zitat Le Bon A, Thompson C, Kamphuis E, Durand V, Rossmann C, Kalinke U, Tough DF (2006) Cutting edge: enhancement of antibody responses through direct stimulation of B and T cells by type I IFN. Journal of immunology 176(4):2074–2078CrossRef Le Bon A, Thompson C, Kamphuis E, Durand V, Rossmann C, Kalinke U, Tough DF (2006) Cutting edge: enhancement of antibody responses through direct stimulation of B and T cells by type I IFN. Journal of immunology 176(4):2074–2078CrossRef
41.
Zurück zum Zitat Nguyen KB, Salazar-Mather TP, Dalod MY, Van Deusen JB, Wei XQ, Liew FY, Caligiuri MA, Durbin JE, Biron CA (2002) Coordinated and distinct roles for IFN-alpha beta, IL-12, and IL-15 regulation of NK cell responses to viral infection. Journal of immunology 169(8):4279–4287CrossRef Nguyen KB, Salazar-Mather TP, Dalod MY, Van Deusen JB, Wei XQ, Liew FY, Caligiuri MA, Durbin JE, Biron CA (2002) Coordinated and distinct roles for IFN-alpha beta, IL-12, and IL-15 regulation of NK cell responses to viral infection. Journal of immunology 169(8):4279–4287CrossRef
42.
Zurück zum Zitat Swann JB, Hayakawa Y, Zerafa N, Sheehan KC, Scott B, Schreiber RD, Hertzog P, Smyth MJ (2007) Type I IFN contributes to NK cell homeostasis, activation, and antitumor function. Journal of immunology 178(12):7540–7549CrossRef Swann JB, Hayakawa Y, Zerafa N, Sheehan KC, Scott B, Schreiber RD, Hertzog P, Smyth MJ (2007) Type I IFN contributes to NK cell homeostasis, activation, and antitumor function. Journal of immunology 178(12):7540–7549CrossRef
43.
Zurück zum Zitat Jonasch E, Haluska FG (2001) Interferon in oncological practice: review of interferon biology, clinical applications, and toxicities. Oncologist 6(1):34–55CrossRefPubMed Jonasch E, Haluska FG (2001) Interferon in oncological practice: review of interferon biology, clinical applications, and toxicities. Oncologist 6(1):34–55CrossRefPubMed
Metadaten
Titel
2′–5′ Oligoadenylate synthetase-like 1 (OASL1) deficiency in mice promotes an effective anti-tumor immune response by enhancing the production of type I interferons
verfasst von
Chan Kyu Sim
Yeon Sook Cho
Byung Soo Kim
In-Jeoung Baek
Young-Joon Kim
Myeong Sup Lee
Publikationsdatum
31.03.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 6/2016
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-016-1830-9

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