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Innate Immune Receptor Signaling and IRF Family of Transcription Factors: Good Deeds and Misdeeds in Oncogenesis

  • Chapter
Inflammation and Immunity in Cancer

Abstract

Harnessing the immune system to control and eradicate cancer has been a major objective for immunologists. Despite much aspiration and effort, decades of frustration have passed following many unsuccessful approaches to induce productive immune responses to “originally self-derived” cancer cells. In recent years, however, significant progress has been made, exemplified by the antibody-mediated blockade of the so-called immune checkpoints. In terms of our understanding of the immune system’s regulation of oncogenesis, there have been advances in how innate immune receptor signaling pathways are involved in the regulation of oncogenesis. The many classes of innate immune receptors and their downstream signaling pathways have been well studied in the context of their role against invading pathogens. The interferon regulatory factor (IRF) family of transcription factors in particular has been described as key downstream regulators of innate receptors. Here, we summarize the yin-yang nature of the innate immune receptors and IRFs in the regulation of oncogenesis.

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Abbreviations

CLR:

C-type lectin receptor

DAMP:

Damage-associated molecular pattern molecule

IFN:

Interferon

IRF:

Interferon regulatory factor

NLR:

NOD-like receptor

PAMP:

Pathogen-associated molecular pattern

PRR:

Pattern recognition receptor

RLR:

RIG-I-like receptor

TAMP:

Tumor-associated molecular pattern

TLR:

Toll-like receptor

References

  • Ahrens S, Zelenay S, Sancho D, Hanc P, Kjaer S, Feest C, Fletcher G, Durkin C, Postigo A, Skehel M, Batista F, Thompson B, Way M, Reis e Sousa C, Schulz O (2012) F-actin is an evolutionarily conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells. Immunity 36(4):635–645. doi:10.1016/j.immuni.2012.03.008

    Article  CAS  PubMed  Google Scholar 

  • Allen IC, TeKippe EM, Woodford RM, Uronis JM, Holl EK, Rogers AB, Herfarth HH, Jobin C, Ting JP (2010) The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med 207(5):1045–1056. doi:10.1084/jem.20100050

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P, Yang H, Amigorena S, Ryffel B, Barrat FJ, Saftig P, Levi F, Lidereau R, Nogues C, Mira JP, Chompret A, Joulin V, Clavel-Chapelon F, Bourhis J, Andre F, Delaloge S, Tursz T, Kroemer G, Zitvogel L (2007) Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13(9):1050–1059. doi:10.1038/nm1622

    Article  CAS  PubMed  Google Scholar 

  • Bailey CM, Abbott DE, Margaryan NV, Khalkhali-Ellis Z, Hendrix MJ (2008) Interferon regulatory factor 6 promotes cell cycle arrest and is regulated by the proteasome in a cell cycle-dependent manner. Mol Cell Biol 28(7):2235–2243. doi:10.1128/MCB. 01866-07

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Barnes BJ, Kellum MJ, Pinder KE, Frisancho JA, Pitha PM (2003) Interferon regulatory factor 5, a novel mediator of cell cycle arrest and cell death. Cancer Res 63(19):6424–6431

    CAS  PubMed  Google Scholar 

  • Bi X, Hameed M, Mirani N, Pimenta EM, Anari J, Barnes BJ (2011) Loss of interferon regulatory factor 5 (IRF5) expression in human ductal carcinoma correlates with disease stage and contributes to metastasis. Breast Cancer Res 13(6):R111. doi:10.1186/bcr3053

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bidwell BN, Slaney CY, Withana NP, Forster S, Cao Y, Loi S, Andrews D, Mikeska T, Mangan NE, Samarajiwa SA, de Weerd NA, Gould J, Argani P, Moller A, Smyth MJ, Anderson RL, Hertzog PJ, Parker BS (2012) Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape. Nat Med 18(8):1224–1231. doi:10.1038/nm.2830

    Article  CAS  PubMed  Google Scholar 

  • Blasius AL, Beutler B (2010) Intracellular toll-like receptors. Immunity 32(3):305–315. doi:10.1016/j.immuni.2010.03.012

    Article  CAS  PubMed  Google Scholar 

  • Brown GD (2006) Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat Rev Immunol 6(1):33–43. doi:10.1038/nri1745

    Article  CAS  PubMed  Google Scholar 

  • Burchert A, Cai D, Hofbauer LC, Samuelsson MK, Slater EP, Duyster J, Ritter M, Hochhaus A, Muller R, Eilers M, Schmidt M, Neubauer A (2004) Interferon consensus sequence binding protein (ICSBP; IRF-8) antagonizes BCR/ABL and down-regulates bcl-2. Blood 103(9):3480–3489. doi:10.1182/blood-2003-08-2970

    Article  CAS  PubMed  Google Scholar 

  • Burdette DL, Monroe KM, Sotelo-Troha K, Iwig JS, Eckert B, Hyodo M, Hayakawa Y, Vance RE (2011) STING is a direct innate immune sensor of cyclic di-GMP. Nature 478(7370):515–518. doi:10.1038/nature10429

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chen GY, Liu M, Wang F, Bertin J, Nunez G (2011) A functional role for Nlrp6 in intestinal inflammation and tumorigenesis. J Immunol 186(12):7187–7194. doi:10.4049/jimmunol.1100412

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chiba S, Ikushima H, Ueki H, Yanai H, Kimura Y, Hangai S, Nishio J, Negishi H, Tamura T, Saijo S, Iwakura Y, Taniguchi T (2014) Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses. eLife 3:e04177. doi:10.7554/eLife.04177

    Article  PubMed Central  PubMed  Google Scholar 

  • Couzinet A, Tamura K, Chen HM, Nishimura K, Wang Z, Morishita Y, Takeda K, Yagita H, Yanai H, Taniguchi T, Tamura T (2008) A cell-type-specific requirement for IFN regulatory factor 5 (IRF5) in Fas-induced apoptosis. Proc Natl Acad Sci U S A 105(7):2556–2561. doi:10.1073/pnas.0712295105

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • del Fresno C, Soulat D, Roth S, Blazek K, Udalova I, Sancho D, Ruland J, Ardavin C (2013) Interferon-beta production via Dectin-1-Syk-IRF5 signaling in dendritic cells is crucial for immunity to C. albicans. Immunity 38(6):1176–1186. doi:10.1016/j.immuni.2013.05.010

    Article  PubMed  Google Scholar 

  • Dror N, Rave-Harel N, Burchert A, Azriel A, Tamura T, Tailor P, Neubauer A, Ozato K, Levi BZ (2007) Interferon regulatory factor-8 is indispensable for the expression of promyelocytic leukemia and the formation of nuclear bodies in myeloid cells. J Biol Chem 282(8):5633–5640. doi:10.1074/jbc.M607825200

    Article  CAS  PubMed  Google Scholar 

  • Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA, Booth CJ, Peaper DR, Bertin J, Eisenbarth SC, Gordon JI, Flavell RA (2011) NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145(5):745–757. doi:10.1016/j.cell.2011.04.022

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fernandez NC, Lozier A, Flament C, Ricciardi-Castagnoli P, Bellet D, Suter M, Perricaudet M, Tursz T, Maraskovsky E, Zitvogel L (1999) Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med 5(4):405–411. doi:10.1038/7403

    Article  CAS  PubMed  Google Scholar 

  • Frontini M, Vijayakumar M, Garvin A, Clarke N (2009) A ChIP-chip approach reveals a novel role for transcription factor IRF1 in the DNA damage response. Nucleic Acids Res 37(4):1073–1085. doi:10.1093/nar/gkn1051

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Geijtenbeek TB, Gringhuis SI (2009) Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol 9(7):465–479. doi:10.1038/nri2569

    Article  CAS  PubMed  Google Scholar 

  • Goodridge HS, Simmons RM, Underhill DM (2007) Dectin-1 stimulation by Candida albicans yeast or zymosan triggers NFAT activation in macrophages and dendritic cells. J Immunol 178(5):3107–3115

    Article  CAS  PubMed  Google Scholar 

  • Gringhuis SI, den Dunnen J, Litjens M, van Het Hof B, van Kooyk Y, Geijtenbeek TB (2007) C-type lectin DC-SIGN modulates Toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappaB. Immunity 26(5):605–616. doi:10.1016/j.immuni.2007.03.012

    Article  CAS  PubMed  Google Scholar 

  • Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Wevers B, Bruijns SC, Geijtenbeek TB (2009) Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk. Nat Immunol 10(2):203–213. doi:10.1038/ni.1692

    Article  CAS  PubMed  Google Scholar 

  • Hao SX, Ren R (2000) Expression of interferon consensus sequence binding protein (ICSBP) is downregulated in Bcr-Abl-induced murine chronic myelogenous leukemia-like disease, and forced coexpression of ICSBP inhibits Bcr-Abl-induced myeloproliferative disorder. Mol Cell Biol 20(4):1149–1161

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Harada H, Kitagawa M, Tanaka N, Yamamoto H, Harada K, Ishihara M, Taniguchi T (1993) Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and −2. Science 259(5097):971–974

    Article  CAS  PubMed  Google Scholar 

  • Heintel D, Zojer N, Schreder M, Strasser-Weippl K, Kainz B, Vesely M, Gisslinger H, Drach J, Gaiger A, Jager U, Ludwig H (2008) Expression of MUM1/IRF4 mRNA as a prognostic marker in patients with multiple myeloma. Leukemia 22(2):441–445. doi:10.1038/sj.leu.2404895

    Article  CAS  PubMed  Google Scholar 

  • Holm CK, Paludan SR, Fitzgerald KA (2013) DNA recognition in immunity and disease. Curr Opin Immunol 25(1):13–18. doi:10.1016/j.coi.2012.12.006

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Honda K, Taniguchi T (2006) IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol 6(9):644–658. doi:10.1038/nri1900

    Article  CAS  PubMed  Google Scholar 

  • Hoving JC, Wilson GJ, Brown GD (2014) Signalling C-type lectin receptors, microbial recognition and immunity. Cell Microbiol 16(2):185–194. doi:10.1111/cmi.12249

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hu G, Mancl ME, Barnes BJ (2005) Signaling through IFN regulatory factor-5 sensitizes p53-deficient tumors to DNA damage-induced apoptosis and cell death. Cancer Res 65(16):7403–7412. doi:10.1158/0008-5472.CAN-05-0583

    Article  CAS  PubMed  Google Scholar 

  • Hu X, Yang D, Zimmerman M, Liu F, Yang J, Kannan S, Burchert A, Szulc Z, Bielawska A, Ozato K, Bhalla K, Liu K (2011) IRF8 regulates acid ceramidase expression to mediate apoptosis and suppresses myelogeneous leukemia. Cancer Res 71(8):2882–2891. doi:10.1158/0008-5472.CAN-10-2493

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Iida S, Rao PH, Butler M, Corradini P, Boccadoro M, Klein B, Chaganti RS, Dalla-Favera R (1997) Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma. Nat Genet 17(2):226–230. doi:10.1038/ng1097-226

    Article  CAS  PubMed  Google Scholar 

  • Ikushima H, Negishi H, Taniguchi T (2013) The IRF family transcription factors at the interface of innate and adaptive immune responses. Cold Spring Harb Symp Quant Biol 78:105–116. doi:10.1101/sqb.2013.78.020321

    Article  PubMed  Google Scholar 

  • Janeway CA Jr, Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197–216. doi:10.1146/annurev.immunol.20.083001.084359

    Article  CAS  PubMed  Google Scholar 

  • Janowski AM, Kolb R, Zhang W, Sutterwala FS (2013) Beneficial and detrimental roles of NLRs in carcinogenesis. Front Immunol 4:370. doi:10.3389/fimmu.2013.00370

    Article  PubMed Central  PubMed  Google Scholar 

  • Kamijo R, Harada H, Matsuyama T, Bosland M, Gerecitano J, Shapiro D, Le J, Koh SI, Kimura T, Green SJ et al (1994) Requirement for transcription factor IRF-1 in NO synthase induction in macrophages. Science 263(5153):1612–1615

    Article  CAS  PubMed  Google Scholar 

  • Kang DC, Gopalkrishnan RV, Wu Q, Jankowsky E, Pyle AM, Fisher PB (2002) mda-5: an interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. Proc Natl Acad Sci U S A 99(2):637–642. doi:10.1073/pnas.022637199

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kang PB, Azad AK, Torrelles JB, Kaufman TM, Beharka A, Tibesar E, DesJardin LE, Schlesinger LS (2005) The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis. J Exp Med 202(7):987–999. doi:10.1084/jem.20051239

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kano A, Haruyama T, Akaike T, Watanabe Y (1999) IRF-1 is an essential mediator in IFN-gamma-induced cell cycle arrest and apoptosis of primary cultured hepatocytes. Biochem Biophys Res Commun 257(3):672–677. doi:10.1006/bbrc.1999.0276

    Article  CAS  PubMed  Google Scholar 

  • Kawai T, Akira S (2011) Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34(5):637–650. doi:10.1016/j.immuni.2011.05.006

    Article  CAS  PubMed  Google Scholar 

  • Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S, Dong J, Newton K, Qu Y, Liu J, Heldens S, Zhang J, Lee WP, Roose-Girma M, Dixit VM (2011) Non-canonical inflammasome activation targets caspase-11. Nature 479(7371):117–121. doi:10.1038/nature10558

    Article  CAS  PubMed  Google Scholar 

  • Kim T, Kim TY, Song YH, Min IM, Yim J, Kim TK (1999) Activation of interferon regulatory factor 3 in response to DNA-damaging agents. J Biol Chem 274(43):30686–30689

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL, Karin M (2009) Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 457(7225):102–106. doi:10.1038/nature07623

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Krelin Y, Voronov E, Dotan S, Elkabets M, Reich E, Fogel M, Huszar M, Iwakura Y, Segal S, Dinarello CA, Apte RN (2007) Interleukin-1beta-driven inflammation promotes the development and invasiveness of chemical carcinogen-induced tumors. Cancer Res 67(3):1062–1071. doi:10.1158/0008-5472.CAN-06-2956

    Article  CAS  PubMed  Google Scholar 

  • Krieg AM (2007) Development of TLR9 agonists for cancer therapy. J Clin Invest 117(5):1184–1194. doi:10.1172/JCI31414

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • LeibundGut-Landmann S, Gross O, Robinson MJ, Osorio F, Slack EC, Tsoni SV, Schweighoffer E, Tybulewicz V, Brown GD, Ruland J, Reis e Sousa C (2007) Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol 8(6):630–638. doi:10.1038/ni1460

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Cao S, Herman LM, Ma X (2003) Differential regulation of interleukin (IL)-12 p35 and p40 gene expression and interferon (IFN)-gamma-primed IL-12 production by IFN regulatory factor 1. J Exp Med 198(8):1265–1276. doi:10.1084/jem.20030026

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Luo JL, Maeda S, Hsu LC, Yagita H, Karin M (2004) Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression. Cancer Cell 6(3):297–305. doi:10.1016/j.ccr.2004.08.012

    Article  CAS  PubMed  Google Scholar 

  • Meacham CE, Morrison SJ (2013) Tumour heterogeneity and cancer cell plasticity. Nature 501(7467):328–337. doi:10.1038/nature12624

    Article  CAS  PubMed  Google Scholar 

  • Medzhitov R, Janeway CA Jr (2002) Decoding the patterns of self and nonself by the innate immune system. Science 296(5566):298–300. doi:10.1126/science.1068883

    Article  CAS  PubMed  Google Scholar 

  • Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T, Taniguchi T (1988) Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell 54(6):903–913

    Article  CAS  PubMed  Google Scholar 

  • Mocsai A, Ruland J, Tybulewicz VL (2010) The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat Rev Immunol 10(6):387–402. doi:10.1038/nri2765

    Article  CAS  PubMed  Google Scholar 

  • Mori T, Anazawa Y, Iiizumi M, Fukuda S, Nakamura Y, Arakawa H (2002) Identification of the interferon regulatory factor 5 gene (IRF-5) as a direct target for p53. Oncogene 21(18):2914–2918. doi:10.1038/sj.onc.1205459

    Article  CAS  PubMed  Google Scholar 

  • Negishi H, Ohba Y, Yanai H, Takaoka A, Honma K, Yui K, Matsuyama T, Taniguchi T, Honda K (2005) Negative regulation of Toll-like-receptor signaling by IRF-4. Proc Natl Acad Sci U S A 102(44):15989–15994. doi:10.1073/pnas.0508327102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Negishi H, Yanai H, Nakajima A, Koshiba R, Atarashi K, Matsuda A, Matsuki K, Miki S, Doi T, Aderem A, Nishio J, Smale ST, Honda K, Taniguchi T (2012) Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. Nat Immunol 13(7):659–666. doi:10.1038/ni.2307

    Article  CAS  PubMed  Google Scholar 

  • Neumann K, Castineiras-Vilarino M, Hockendorf U, Hannesschlager N, Lemeer S, Kupka D, Meyermann S, Lech M, Anders HJ, Kuster B, Busch DH, Gewies A, Naumann R, Gross O, Ruland J (2014) Clec12a is an inhibitory receptor for uric acid crystals that regulates inflammation in response to cell death. Immunity 40(3):389–399. doi:10.1016/j.immuni.2013.12.015

    Article  CAS  PubMed  Google Scholar 

  • Nguyen H, Mustafa A, Hiscott J, Lin R (1995) Transcription factor IRF-2 exerts its oncogenic phenotype through the DNA binding/transcription repression domain. Oncogene 11(3):537–544

    CAS  PubMed  Google Scholar 

  • Normand S, Delanoye-Crespin A, Bressenot A, Huot L, Grandjean T, Peyrin-Biroulet L, Lemoine Y, Hot D, Chamaillard M (2011) Nod-like receptor pyrin domain-containing protein 6 (NLRP6) controls epithelial self-renewal and colorectal carcinogenesis upon injury. Proc Natl Acad Sci U S A 108(23):9601–9606. doi:10.1073/pnas.1100981108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pamment J, Ramsay E, Kelleher M, Dornan D, Ball KL (2002) Regulation of the IRF-1 tumour modifier during the response to genotoxic stress involves an ATM-dependent signalling pathway. Oncogene 21(51):7776–7785. doi:10.1038/sj.onc.1205981

    Article  CAS  PubMed  Google Scholar 

  • Pettersson S, Kelleher M, Pion E, Wallace M, Ball KL (2009) Role of Mdm2 acid domain interactions in recognition and ubiquitination of the transcription factor IRF-2. Biochem J 418(3):575–585. doi:10.1042/BJ20082087

    Article  CAS  PubMed  Google Scholar 

  • Pradere JP, Dapito DH, Schwabe RF (2014) The Yin and Yang of Toll-like receptors in cancer. Oncogene 33(27):3485–3495. doi:10.1038/onc.2013.302

    Article  CAS  PubMed  Google Scholar 

  • Rakoff-Nahoum S, Medzhitov R (2007) Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88. Science 317(5834):124–127. doi:10.1126/science.1140488

    Article  CAS  PubMed  Google Scholar 

  • Rakoff-Nahoum S, Medzhitov R (2009) Toll-like receptors and cancer. Nat Rev Cancer 9(1):57–63. doi:10.1038/nrc2541

    Article  CAS  PubMed  Google Scholar 

  • Reed JR, Leon RP, Hall MK, Schwertfeger KL (2009) Interleukin-1beta and fibroblast growth factor receptor 1 cooperate to induce cyclooxygenase-2 during early mammary tumourigenesis. Breast Cancer Res 11(2):R21. doi:10.1186/bcr2246

    Article  PubMed Central  PubMed  Google Scholar 

  • Restifo NP, Dudley ME, Rosenberg SA (2012) Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol 12(4):269–281. doi:10.1038/nri3191

    Article  CAS  PubMed  Google Scholar 

  • Rogers NC, Slack EC, Edwards AD, Nolte MA, Schulz O, Schweighoffer E, Williams DL, Gordon S, Tybulewicz VL, Brown GD, Reis e Sousa C (2005) Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity 22(4):507–517. doi:10.1016/j.immuni.2005.03.004

    Article  CAS  PubMed  Google Scholar 

  • Rubartelli A, Lotze MT (2007) Inside, outside, upside down: damage-associated molecular-pattern molecules (DAMPs) and redox. Trends Immunol 28(10):429–436. doi:10.1016/j.it.2007.08.004

    Article  CAS  PubMed  Google Scholar 

  • Saijo Y, Tanaka M, Miki M, Usui K, Suzuki T, Maemondo M, Hong X, Tazawa R, Kikuchi T, Matsushima K, Nukiwa T (2002) Proinflammatory cytokine IL-1 beta promotes tumor growth of Lewis lung carcinoma by induction of angiogenic factors: in vivo analysis of tumor-stromal interaction. J Immunol 169(1):469–475

    Article  CAS  PubMed  Google Scholar 

  • Sancho D, Reis e Sousa C (2012) Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu Rev Immunol 30:491–529. doi:10.1146/annurev-immunol-031210-101352

    Article  CAS  PubMed  Google Scholar 

  • Schroder K, Tschopp J (2010) The inflammasomes. Cell 140(6):821–832. doi:10.1016/j.cell.2010.01.040

    Article  CAS  PubMed  Google Scholar 

  • Shaffer AL, Emre NC, Lamy L, Ngo VN, Wright G, Xiao W, Powell J, Dave S, Yu X, Zhao H, Zeng Y, Chen B, Epstein J, Staudt LM (2008) IRF4 addiction in multiple myeloma. Nature 454(7201):226–231. doi:10.1038/nature07064

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shi Y, Evans JE, Rock KL (2003) Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425(6957):516–521. doi:10.1038/nature01991

    Article  CAS  PubMed  Google Scholar 

  • Slack EC, Robinson MJ, Hernanz-Falcon P, Brown GD, Williams DL, Schweighoffer E, Tybulewicz VL, Reis e Sousa C (2007) Syk-dependent ERK activation regulates IL-2 and IL-10 production by DC stimulated with zymosan. Eur J Immunol 37(6):1600–1612. doi:10.1002/eji.200636830

    Article  CAS  PubMed  Google Scholar 

  • Sun L, Wu J, Du F, Chen X, Chen ZJ (2013) Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339(6121):786–791. doi:10.1126/science.1232458

    Article  CAS  PubMed  Google Scholar 

  • Tailleux L, Schwartz O, Herrmann JL, Pivert E, Jackson M, Amara A, Legres L, Dreher D, Nicod LP, Gluckman JC, Lagrange PH, Gicquel B, Neyrolles O (2003) DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells. J Exp Med 197(1):121–127

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, Sasaki S, Imai K, Shibue T, Honda K, Taniguchi T (2003) Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature 424(6948):516–523. doi:10.1038/nature01850

    Article  CAS  PubMed  Google Scholar 

  • Takaoka A, Yanai H, Kondo S, Duncan G, Negishi H, Mizutani T, Kano S, Honda K, Ohba Y, Mak TW, Taniguchi T (2005) Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 434(7030):243–249. doi:10.1038/nature03308

    Article  CAS  PubMed  Google Scholar 

  • Takaoka A, Wang Z, Choi MK, Yanai H, Negishi H, Ban T, Lu Y, Miyagishi M, Kodama T, Honda K, Ohba Y, Taniguchi T (2007) DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 448(7152):501–505. doi:10.1038/nature06013

    Article  CAS  PubMed  Google Scholar 

  • Tamura T, Ishihara M, Lamphier MS, Tanaka N, Oishi I, Aizawa S, Matsuyama T, Mak TW, Taki S, Taniguchi T (1995) An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes. Nature 376(6541):596–599. doi:10.1038/376596a0

    Article  CAS  PubMed  Google Scholar 

  • Tamura T, Kong HJ, Tunyaplin C, Tsujimura H, Calame K, Ozato K (2003) ICSBP/IRF-8 inhibits mitogenic activity of p210 Bcr/Abl in differentiating myeloid progenitor cells. Blood 102(13):4547–4554. doi:10.1182/blood-2003-01-0291

    Article  CAS  PubMed  Google Scholar 

  • Tamura T, Yanai H, Savitsky D, Taniguchi T (2008) The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol 26:535–584. doi:10.1146/annurev.immunol.26.021607.090400

    Article  CAS  PubMed  Google Scholar 

  • Tanaka N, Ishihara M, Kitagawa M, Harada H, Kimura T, Matsuyama T, Lamphier MS, Aizawa S, Mak TW, Taniguchi T (1994) Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1. Cell 77(6):829–839

    Article  CAS  PubMed  Google Scholar 

  • Tanaka N, Ishihara M, Lamphier MS, Nozawa H, Matsuyama T, Mak TW, Aizawa S, Tokino T, Oren M, Taniguchi T (1996) Cooperation of the tumour suppressors IRF-1 and p53 in response to DNA damage. Nature 382(6594):816–818. doi:10.1038/382816a0

    Article  CAS  PubMed  Google Scholar 

  • Taylor PR, Brown GD, Reid DM, Willment JA, Martinez-Pomares L, Gordon S, Wong SY (2002) The beta-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. J Immunol 169(7):3876–3882

    Article  CAS  PubMed  Google Scholar 

  • Tsujimura H, Tamura T, Kong HJ, Nishiyama A, Ishii KJ, Klinman DM, Ozato K (2004) Toll-like receptor 9 signaling activates NF-kappaB through IFN regulatory factor-8/IFN consensus sequence binding protein in dendritic cells. J Immunol 172(11):6820–6827

    Article  CAS  PubMed  Google Scholar 

  • Underhill DM, Rossnagle E, Lowell CA, Simmons RM (2005) Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. Blood 106(7):2543–2550. doi:10.1182/blood-2005-03-1239

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Unterholzner L, Keating SE, Baran M, Horan KA, Jensen SB, Sharma S, Sirois CM, Jin T, Latz E, Xiao TS, Fitzgerald KA, Paludan SR, Bowie AG (2010) IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol 11(11):997–1004. doi:10.1038/ni.1932

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Voronov E, Shouval DS, Krelin Y, Cagnano E, Benharroch D, Iwakura Y, Dinarello CA, Apte RN (2003) IL-1 is required for tumor invasiveness and angiogenesis. Proc Natl Acad Sci U S A 100(5):2645–2650. doi:10.1073/pnas.0437939100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Weihua X, Lindner DJ, Kalvakolanu DV (1997) The interferon-inducible murine p48 (ISGF3gamma) gene is regulated by protooncogene c-myc. Proc Natl Acad Sci U S A 94(14):7227–7232

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yamasaki S, Ishikawa E, Sakuma M, Hara H, Ogata K, Saito T (2008) Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nat Immunol 9(10):1179–1188. doi:10.1038/ni.1651

    Article  CAS  PubMed  Google Scholar 

  • Yanai H, Chen HM, Inuzuka T, Kondo S, Mak TW, Takaoka A, Honda K, Taniguchi T (2007) Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression. Proc Natl Acad Sci U S A 104(9):3402–3407. doi:10.1073/pnas.0611559104

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yanai H, Ban T, Wang Z, Choi MK, Kawamura T, Negishi H, Nakasato M, Lu Y, Hangai S, Koshiba R, Savitsky D, Ronfani L, Akira S, Bianchi ME, Honda K, Tamura T, Kodama T, Taniguchi T (2009) HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature 462(7269):99–103. doi:10.1038/nature08512

    Article  CAS  PubMed  Google Scholar 

  • Yanai H, Negishi H, Taniguchi T (2012) The IRF family of transcription factors: Inception, impact and implications in oncogenesis. OncoImmunology 1(8):1376–1386. doi:10.4161/onci.22475

    Article  PubMed Central  PubMed  Google Scholar 

  • Yang L, Zhao T, Shi X, Nakhaei P, Wang Y, Sun Q, Hiscott J, Lin R (2009) Functional analysis of a dominant negative mutation of interferon regulatory factor 5. PLoS One 4(5):e5500. doi:10.1371/journal.pone.0005500

    Article  PubMed Central  PubMed  Google Scholar 

  • Yin Q, Tian Y, Kabaleeswaran V, Jiang X, Tu D, Eck MJ, Chen ZJ, Wu H (2012) Cyclic di-GMP sensing via the innate immune signaling protein STING. Mol Cell 46(6):735–745. doi:10.1016/j.molcel.2012.05.029

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yokoyama WM, Plougastel BF (2003) Immune functions encoded by the natural killer gene complex. Nat Rev Immunol 3(4):304–316. doi:10.1038/nri1055

    Article  CAS  PubMed  Google Scholar 

  • Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5(7):730–737. doi:10.1038/ni1087

    Article  CAS  PubMed  Google Scholar 

  • Zaki MH, Vogel P, Body-Malapel M, Lamkanfi M, Kanneganti TD (2010) IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation. J Immunol 185(8):4912–4920. doi:10.4049/jimmunol.1002046

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang JG, Czabotar PE, Policheni AN, Caminschi I, Wan SS, Kitsoulis S, Tullett KM, Robin AY, Brammananth R, van Delft MF, Lu J, O’Reilly LA, Josefsson EC, Kile BT, Chin WJ, Mintern JD, Olshina MA, Wong W, Baum J, Wright MD, Huang DC, Mohandas N, Coppel RL, Colman PM, Nicola NA, Shortman K, Lahoud MH (2012) The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments. Immunity 36(4):646–657. doi:10.1016/j.immuni.2012.03.009

    Article  CAS  PubMed  Google Scholar 

  • Zitvogel L, Kepp O, Galluzzi L, Kroemer G (2012) Inflammasomes in carcinogenesis and anticancer immune responses. Nat Immunol 13(4):343–351. doi:10.1038/ni.2224

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to apologize to all of the authors whose invaluable work we could not discuss or cite in this chapter due to space constraints. Our work was supported in part by the Core Research for Evolutional Science and Technology (CREST) of JST, a Grant-in-Aid for Exploratory Research of MEXT, and a Grant-In-Aid for Scientific Research on Innovative Areas of MEXT.

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Authors and Affiliations

  1. Department of Molecular Immunology, Institute of Industrial Science, Max Planck-The University of Tokyo Center for Integrative Inflammology, The University of Tokyo, Komaba 4-6-1, Meguro-ku, Tokyo, 153-8505, Japan

    Hiroaki Ikushima, Hideyuki Yanai & Tadatsugu Taniguchi

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  1. Hiroaki Ikushima
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  2. Hideyuki Yanai
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  3. Tadatsugu Taniguchi
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Correspondence to Tadatsugu Taniguchi .

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Editors and Affiliations

  1. Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan

    Tsukasa Seya

  2. Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan

    Misako Matsumoto

  3. Kochi Medical School, Kochi University, Nankoku, Kochi, Japan

    Keiko Udaka

  4. School of Medicine, Sapporo Medical University, Sapporo, Hokkaido, Japan

    Noriyuki Sato

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Ikushima, H., Yanai, H., Taniguchi, T. (2015). Innate Immune Receptor Signaling and IRF Family of Transcription Factors: Good Deeds and Misdeeds in Oncogenesis. In: Seya, T., Matsumoto, M., Udaka, K., Sato, N. (eds) Inflammation and Immunity in Cancer. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55327-4_7

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