Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2017, Article ID 3958069, 14 pages
https://doi.org/10.1155/2017/3958069
Review Article

Dual Roles of IL-27 in Cancer Biology and Immunotherapy

Laboratory of Biotherapy, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genoa, Italy

Correspondence should be addressed to Silvano Ferrini; ti.orebil@inirref.onavlis

Received 31 October 2016; Revised 23 December 2016; Accepted 12 January 2017; Published 1 February 2017

Academic Editor: Dmitri V. Krysko

Copyright © 2017 Marina Fabbi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. Snyder, D. Zamarin, and J. D. Wolchok, “Immunotherapy of Melanoma,” Progress in Tumor Research, vol. 42, pp. 22–29, 2015. View at Publisher · View at Google Scholar · View at Scopus
  2. S. A. Rosenberg, “IL-2: the first effective immunotherapy for human cancer,” The Journal of Immunology, vol. 192, no. 12, pp. 5451–5458, 2014. View at Publisher · View at Google Scholar · View at Scopus
  3. F. S. Hodi, S. J. O'Day, D. F. McDermott et al., “Improved survival with ipilimumab in patients with metastatic melanoma,” New England Journal of Medicine, vol. 363, no. 8, pp. 711–723, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. J. S. Weber, S. P. D'Angelo, D. Minor et al., “Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial,” The Lancet Oncology, vol. 16, no. 4, pp. 375–384, 2015. View at Publisher · View at Google Scholar · View at Scopus
  5. C. Robert, J. Schachter, G. V. Long et al., “Pembrolizumab versus ipilimumab in advanced melanoma,” New England Journal of Medicine, vol. 372, no. 26, pp. 2521–2532, 2015. View at Publisher · View at Google Scholar · View at Scopus
  6. A. M. M. Eggermont, M. Maio, and C. Robert, “Immune checkpoint inhibitors in melanoma provide the cornerstones for curative therapies,” Seminars in Oncology, vol. 42, no. 3, pp. 429–435, 2015. View at Publisher · View at Google Scholar · View at Scopus
  7. P. C. Tumeh, C. L. Harview, J. H. Yearley et al., “PD-1 blockade induces responses by inhibiting adaptive immune resistance,” Nature, vol. 515, no. 7528, pp. 568–571, 2014. View at Publisher · View at Google Scholar · View at Scopus
  8. S. L. Topalian, C. G. Drake, and D. M. Pardoll, “Immune checkpoint blockade: a common denominator approach to cancer therapy,” Cancer Cell, vol. 27, no. 4, pp. 451–461, 2015. View at Publisher · View at Google Scholar · View at Scopus
  9. T. Okazaki, S. Chikuma, Y. Iwai, S. Fagarasan, and T. Honjo, “A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application,” Nature Immunology, vol. 14, no. 12, pp. 1212–1218, 2013. View at Publisher · View at Google Scholar · View at Scopus
  10. K. Pilipow, A. Roberto, M. Roederer, T. A. Waldmann, D. Mavilio, and E. Lugli, “IL15 and T-cell stemness in T-cell-based cancer immunotherapy,” Cancer Research, vol. 75, no. 24, pp. 5187–5193, 2015. View at Publisher · View at Google Scholar · View at Scopus
  11. M. Croce, A. M. Orengo, B. Azzarone, and S. Ferrini, “Immunotherapeutic applications of IL-15,” Immunotherapy, vol. 4, no. 9, pp. 957–969, 2012. View at Publisher · View at Google Scholar · View at Scopus
  12. T. Floros and A. A. Tarhini, “Anticancer cytokines: biology and clinical effects of interferon-α2, interleukin (IL)-2, IL-15, IL-21, and IL-12,” Seminars in Oncology, vol. 42, no. 4, pp. 539–548, 2015. View at Publisher · View at Google Scholar · View at Scopus
  13. R. Spolski and W. J. Leonard, “Interleukin-21: a double-edged sword with therapeutic potential,” Nature Reviews Drug Discovery, vol. 13, no. 5, pp. 379–395, 2014. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Croce, V. Rigo, and S. Ferrini, “IL-21: a pleiotropic cytokine with potential applications in oncology,” Journal of Immunology Research, vol. 2015, Article ID 696578, 15 pages, 2015. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Fabbi, G. Carbotti, and S. Ferrini, “Context-dependent role of IL-18 in cancer biology and counter-regulation by IL-18BP,” Journal of Leukocyte Biology, vol. 97, no. 4, pp. 665–675, 2015. View at Publisher · View at Google Scholar · View at Scopus
  16. M. J. Robertson, J. M. Kirkwood, T. F. Logan et al., “A dose-escalation study of recombinant human interleukin-18 using two different schedules of administration in patients with cancer,” Clinical Cancer Research, vol. 14, no. 11, pp. 3462–3469, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. T. M. Petrella, R. Tozer, K. Belanger et al., “Interleukin-21 has activity in patients with metastatic melanoma: a phase II study,” Journal of Clinical Oncology, vol. 30, no. 27, pp. 3396–3401, 2012. View at Publisher · View at Google Scholar · View at Scopus
  18. E. Di Carlo, A. Comes, A. M. Orengo et al., “IL-21 induces tumor rejection by specific CTL and IFN-γ-dependent CXC chemokines in syngeneic mice,” The Journal of Immunology, vol. 172, no. 3, pp. 1540–1547, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. G. Monteleone, M. Sarra, and F. Pallone, “Interleukin-21 in T cell-mediated diseases,” Discovery Medicine, vol. 8, no. 42, pp. 113–117, 2009. View at Google Scholar · View at Scopus
  20. R. Spolski, H.-P. Kim, W. Zhu, D. E. Levy, and W. J. Leonard, “IL-21 mediates suppressive effects via its induction of IL-10,” Journal of Immunology, vol. 182, no. 5, pp. 2859–2867, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Zorzoli, E. Di Carlo, C. Cocco et al., “Interleukin-27 inhibits the growth of pediatric acute myeloid leukemia in NOD/SCID/Il2rg-/- mice,” Clinical Cancer Research, vol. 18, no. 6, pp. 1630–1640, 2012. View at Publisher · View at Google Scholar
  22. I. Airoldi, M. G. Tupone, S. Esposito et al., “Interleukin-27 re-educates intratumoral myeloid cells and down-regulates stemness genes in non-small cell lung cancer,” Oncotarget, vol. 6, no. 6, pp. 3694–3708, 2015. View at Publisher · View at Google Scholar · View at Scopus
  23. E. Di Carlo, C. Sorrentino, A. Zorzoli et al., “The antitumor potential of Interleukin-27 in prostate cancer,” Oncotarget, vol. 5, no. 21, pp. 10332–10341, 2014. View at Publisher · View at Google Scholar · View at Scopus
  24. C. Cocco, N. Giuliani, E. Di Carlo et al., “Interleukin-27 acts as multifunctional antitumor agent in multiple myeloma,” Clinical Cancer Research, vol. 16, no. 16, pp. 4188–4197, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. A. Petretto, G. Carbotti, E. Inglese, C. Lavarello, M. P. Pistillo, and V. Rigo, “Proteomic analysis uncovers common effects of IFN-gamma and IL-27 on the HLA class I antigen presentation machinery in human cancer cells,” Oncotarget, vol. 7, no. 45, pp. 72518–72536, 2016. View at Google Scholar
  26. Z. Zhang, B. Zhou, K. Zhang, Y. Song, L. Zhang, and M. Xi, “IL-27 suppresses SKOV3 cells proliferation by enhancing STAT3 and inhibiting the Akt signal pathway,” Molecular Immunology, vol. 78, pp. 155–163, 2016. View at Publisher · View at Google Scholar
  27. M. H. Lee, P. Kachroo, P. C. Pagano et al., “Combination treatment with apricoxib and IL-27 enhances inhibition of epithelial-mesenchymal transition in human lung cancer cells through a STAT1 dominant pathway,” Journal of Cancer Science & Therapy, vol. 6, no. 11, pp. 468–477, 2014. View at Publisher · View at Google Scholar
  28. P. Kachroo, M.-H. Lee, L. Zhang et al., “IL-27 inhibits epithelial-mesenchymal transition and angiogenic factor production in a STAT1-dominant pathway in human non-small cell lung cancer,” Journal of Experimental and Clinical Cancer Research, vol. 32, article 97, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. T. Yoshimoto, N. Morishima, I. Mizoguchi et al., “Antiproliferative activity of IL-27 on melanoma,” The Journal of Immunology, vol. 180, no. 10, pp. 6527–6535, 2008. View at Publisher · View at Google Scholar · View at Scopus
  30. Y. Chiba, I. Mizoguchi, K. Mitobe et al., “IL-27 enhances the expression of TRAIL and TLR3 in human melanomas and inhibits their tumor growth in cooperation with a TLR3 agonist Poly(I:C) partly in a TRAIL-dependent manner,” PLoS ONE, vol. 8, no. 10, Article ID e76159, 2013. View at Publisher · View at Google Scholar · View at Scopus
  31. M. Shimizu, M. Shimamura, T. Owaki et al., “Antiangiogenic and antitumor activities of IL-27,” Journal of Immunology, vol. 176, no. 12, pp. 7317–7324, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. S. A. Dorosz, A. Ginolhac, T. Kähne et al., “Role of calprotectin as a modulator of the IL27-mediated proinflammatory effect on endothelial cells,” Mediators of Inflammation, vol. 2015, Article ID 737310, 16 pages, 2015. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Hisada, S. Kamiya, K. Fujita et al., “Potent antitumor activity of interleukin-27,” Cancer Research, vol. 64, no. 3, pp. 1152–1156, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. R. Salcedo, J. K. Stauffer, E. Lincoln et al., “IL-27 mediates complete regression of orthotopic primary and metastatic murine neuroblastoma tumors: role for CD8+ T cells,” The Journal of Immunology, vol. 173, no. 12, pp. 7170–7182, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. R. Salcedo, J. A. Hixon, J. K. Stauffer et al., “Immunologic and therapeutic synergy of IL-27 and IL-2: enhancement of T cell sensitization, tumor-specific CTL reactivity and complete regression of disseminated neuroblastoma metastases in the liver and bone marrow,” The Journal of Immunology, vol. 182, no. 7, pp. 4328–4338, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Matsui, T. Kishida, H. Nakano et al., “Interleukin-27 activates natural killer cells and suppresses NK-resistant head and neck squamous cell carcinoma through inducing antibody-dependent cellular cytotoxicity,” Cancer Research, vol. 69, no. 6, pp. 2523–2530, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. L. Liu, S. Wang, B. Shan et al., “IL-27-mediated activation of natural killer cells and inflammation produced antitumour effects for human oesophageal carcinoma cells,” Scandinavian Journal of Immunology, vol. 68, no. 1, pp. 22–29, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. L. Yao, M. Wang, Z. Niu et al., “Interleukin-27 inhibits malignant behaviors of pancreatic cancer cells by targeting M2 polarized tumor associated macrophages,” Cytokine, vol. 89, pp. 194–200, 2017. View at Publisher · View at Google Scholar · View at Scopus
  39. D. Dibra, A. Mitra, M. Newman et al., “Lack of immunomodulatory interleukin-27 enhances oncogenic properties of mutant p53 in vivo,” Clinical Cancer Research, vol. 22, no. 15, pp. 3876–3883, 2016. View at Publisher · View at Google Scholar · View at Scopus
  40. Z. Liu, J.-Q. Liu, Y. Shi et al., “Epstein-Barr virus-induced gene 3-deficiency leads to impaired antitumor T-cell responses and accelerated tumor growth,” OncoImmunology, vol. 4, no. 7, Article ID e989137, 2015. View at Publisher · View at Google Scholar · View at Scopus
  41. H. Jia, P. Dilger, C. Bird, and M. Wadhwa, “IL-27 promotes proliferation of human leukemic cell lines through the MAPK/ERK signaling pathway and suppresses sensitivity to chemotherapeutic drugs,” Journal of Interferon and Cytokine Research, vol. 36, no. 5, pp. 302–316, 2016. View at Publisher · View at Google Scholar · View at Scopus
  42. G. Carbotti, G. Barisione, I. Airoldi et al., “IL-27 induces the expression of IDO and PD-L1 in human cancer cells,” Oncotarget, vol. 6, no. 41, pp. 43267–43280, 2015. View at Publisher · View at Google Scholar · View at Scopus
  43. G. Carbotti, G. Barisione, A. M. Orengo et al., “The IL-18 antagonist IL-18-binding protein is produced in the human ovarian cancer microenvironment,” Clinical Cancer Research, vol. 19, no. 17, pp. 4611–4620, 2013. View at Publisher · View at Google Scholar · View at Scopus
  44. S. M. d'Almeida, G. Kauffenstein, C. Roy et al., “The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: regulatory role of IL-27,” OncoImmunology, vol. 5, no. 7, Article ID e1178025, 2016. View at Publisher · View at Google Scholar · View at Scopus
  45. H. Horlad, C. Ma, H. Yano et al., “An IL-27/Stat3 axis induces expression of programmed cell death 1 ligands (PD-L1/2) on infiltrating macrophages in lymphoma,” Cancer Science, vol. 107, no. 11, pp. 1696–1704, 2016. View at Publisher · View at Google Scholar
  46. C. Zhu, K. Sakuishi, S. Xiao et al., “An IL-27/NFIL3 signalling axis drives tim-3 and IL-10 expression and T-cell dysfunction,” Nature Communications, vol. 6, article 6072, 2015. View at Publisher · View at Google Scholar
  47. H. Yoshida and C. A. Hunter, “The immunobiology of interleukin-27,” Annual Review of Immunology, vol. 33, pp. 417–443, 2015. View at Publisher · View at Google Scholar · View at Scopus
  48. T. Yoshimoto, Y. Chiba, J.-I. Furusawa et al., “Potential clinical application of interleukin-27 as an antitumor agent,” Cancer Science, vol. 106, no. 9, pp. 1103–1110, 2015. View at Publisher · View at Google Scholar · View at Scopus
  49. M.-S. Li, Z. Liu, J.-Q. Liu, X. Zhu, Z. Liu, and X.-F. Bai, “The Yin and Yang aspects of IL-27 in induction of cancer-specific T-cell responses and immunotherapy,” Immunotherapy, vol. 7, no. 2, pp. 191–200, 2015. View at Publisher · View at Google Scholar · View at Scopus
  50. G. Trinchieri, S. Pflanz, and R. A. Kastelein, “The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses,” Immunity, vol. 19, no. 5, pp. 641–644, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. D. A. A. Vignali and V. K. Kuchroo, “IL-12 family cytokines: immunological playmakers,” Nature Immunology, vol. 13, no. 8, pp. 722–728, 2012. View at Publisher · View at Google Scholar · View at Scopus
  52. S. Pflanz, J. C. Timans, J. Cheung et al., “IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells,” Immunity, vol. 16, no. 6, pp. 779–790, 2002. View at Publisher · View at Google Scholar · View at Scopus
  53. O. Devergne, M. Birkenbach, and E. Kieff, “Epstein-Barr virus-induced gene 3 and the p35 subunit of interleukin 12 form a novel heterodimeric hematopoietin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 22, pp. 12041–12046, 1997. View at Publisher · View at Google Scholar · View at Scopus
  54. L. W. Collison, C. J. Workman, T. T. Kuo et al., “The inhibitory cytokine IL-35 contributes to regulatory T-cell function,” Nature, vol. 450, no. 7169, pp. 566–569, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. R.-X. Wang, C.-R. Yu, I. M. Dambuza et al., “Interleukin-35 induces regulatory B cells that suppress autoimmune disease,” Nature Medicine, vol. 20, no. 6, pp. 633–641, 2014. View at Publisher · View at Google Scholar · View at Scopus
  56. P. Shen, T. Roch, V. Lampropoulou et al., “IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases,” Nature, vol. 507, no. 7492, pp. 366–370, 2014. View at Publisher · View at Google Scholar · View at Scopus
  57. X. Wang, Y. Wei, H. Xiao et al., “A novel IL-23p19/Ebi3 (IL-39) cytokine mediates inflammation in Lupus-like mice,” European Journal of Immunology, vol. 46, no. 6, pp. 1343–1350, 2016. View at Publisher · View at Google Scholar · View at Scopus
  58. S. Crabé, A. Guay-Giroux, A. J. Tormo et al., “The IL-27 p28 subunit binds cytokine-like factor 1 to form a cytokine regulating NK and T cell activities requiring IL-6R for signaling,” The Journal of Immunology, vol. 183, no. 12, pp. 7692–7702, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. S. Pflanz, L. Hibbert, J. Mattson et al., “WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27,” Journal of Immunology, vol. 172, no. 4, pp. 2225–2231, 2004. View at Publisher · View at Google Scholar · View at Scopus
  60. L. W. Collison, G. M. Delgoffe, C. S. Guy et al., “The composition and signaling of the IL-35 receptor are unconventional,” Nature Immunology, vol. 13, no. 3, pp. 290–299, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. C. Garbers, H. M. Hermanns, F. Schaper et al., “Plasticity and cross-talk of interleukin 6-type cytokines,” Cytokine and Growth Factor Reviews, vol. 23, no. 3, pp. 85–97, 2012. View at Publisher · View at Google Scholar · View at Scopus
  62. A. J. Tormo, Y. Meliani, L. A. Beaupré et al., “The composite cytokine p28/cytokine-like factor 1 sustains B cell proliferation and promotes plasma cell differentiation,” Journal of Immunology, vol. 191, no. 4, pp. 1657–1665, 2013. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Jankowski, P. Kopiński, and A. Goc, “Interleukin-27: biological properties and clinical application,” Archivum Immunologiae et Therapiae Experimentalis, vol. 58, no. 6, pp. 417–425, 2010. View at Publisher · View at Google Scholar
  64. D. Dibra, J. J. Cutrera, X. Xia, M. P. Birkenbach, and S. Li, “Expression of WSX1 in tumors sensitizes IL-27 signaling-independent natural killer cell surveillance,” Cancer Research, vol. 69, no. 13, pp. 5505–5513, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. C. Molle, M. Nguyen, V. Flamand et al., “IL-27 synthesis induced by TLR ligation critically depends on IFN regulatory factor 3,” The Journal of Immunology, vol. 178, no. 12, pp. 7607–7615, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. N. D. Pennock, L. Gapin, and R. M. Kedl, “IL-27 is required for shaping the magnitude, affinity distribution, and memory of T cells responding to subunit immunization,” Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 46, pp. 16472–16477, 2014. View at Publisher · View at Google Scholar · View at Scopus
  67. M. E. Remoli, V. Gafa, E. Giacomini, M. Severa, R. Lande, and E. M. Coccia, “IFN-β modulates the response to TLR stimulation in human DC: involvement of IFN regulatory factor-1 (IRF-1) in IL-27 gene expression,” European Journal of Immunology, vol. 37, no. 12, pp. 3499–3508, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. J. Liu, X. Guan, and X. Ma, “Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-γ-mediated pathways,” Journal of Experimental Medicine, vol. 204, no. 1, pp. 141–152, 2007. View at Publisher · View at Google Scholar · View at Scopus
  69. D. Kimura, M. Miyakoda, K. Kimura et al., “Interleukin-27-producing CD4+ T cells regulate protective immunity during malaria parasite infection,” Immunity, vol. 44, no. 3, pp. 672–682, 2016. View at Publisher · View at Google Scholar · View at Scopus
  70. J. S. Stumhofer, E. D. Tait, W. J. Q. Iii et al., “A role for IL-27p28 as an antagonist of gp130-mediated signaling,” Nature Immunology, vol. 11, no. 12, pp. 1119–1126, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. O. Shimozato, A. Sato, K. Kawamura et al., “The secreted form of p28 subunit of interleukin (IL)-27 inhibits biological functions of IL-27 and suppresses anti-allogeneic immune responses,” Immunology, vol. 128, no. 1, pp. e816–e825, 2009. View at Publisher · View at Google Scholar · View at Scopus
  72. C. Garbers, B. Spudy, S. Aparicio-Siegmund et al., “An lnterleukin-6 receptor-dependent molecular switch mediates signal transduction of the IL-27 cytokine subunit p28 (IL-30) via a gp130 protein receptor homodimer,” Journal of Biological Chemistry, vol. 288, no. 6, pp. 4346–4354, 2013. View at Publisher · View at Google Scholar · View at Scopus
  73. S. Rose-John and P. C. Heinrich, “Soluble receptors for cytokines and growth factors: generation and biological function,” Biochemical Journal, vol. 300, no. 2, part 2, pp. 281–290, 1994. View at Publisher · View at Google Scholar · View at Scopus
  74. M. Fischer, J. Goldschmitt, C. Peschel et al., “A bioactive designer cytokine for human hematopoietic progenitor cell expansion,” Nature Biotechnology, vol. 15, no. 2, pp. 142–145, 1997. View at Publisher · View at Google Scholar · View at Scopus
  75. J. Scheller, B. Schuster, C. Hölscher, T. Yoshimoto, and S. Rose-John, “No inhibition of IL-27 signaling by soluble gp130,” Biochemical and Biophysical Research Communications, vol. 326, no. 4, pp. 724–728, 2005. View at Publisher · View at Google Scholar · View at Scopus
  76. J. Lokau, R. Nitz, M. Agthe et al., “Proteolytic cleavage governs interleukin-11 trans-signaling,” Cell Reports, vol. 14, no. 7, pp. 1761–1773, 2016. View at Publisher · View at Google Scholar · View at Scopus
  77. L. Hibbert, S. Pflanz, R. De Waal Malefyt, and R. A. Kastelein, “IL-27 and IFN-α signal via Stat1 and Stat3 and induce T-Bet and IL-12Rβ2 in naive T cells,” Journal of Interferon and Cytokine Research, vol. 23, no. 9, pp. 513–522, 2003. View at Publisher · View at Google Scholar · View at Scopus
  78. C. Brender, G. M. Tannahill, B. J. Jenkins et al., “Suppressor of cytokine signaling 3 regulates CD8 T-cell proliferation by inhibition of interleukins 6 and 27,” Blood, vol. 110, no. 7, pp. 2528–2536, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. C. Dietrich, S. Candon, F. M. Ruemmele, and O. Devergne, “A soluble form of IL-27Rα is a natural IL-27 antagonist,” The Journal of Immunology, vol. 192, no. 11, pp. 5382–5389, 2014. View at Publisher · View at Google Scholar · View at Scopus
  80. S. Wirtz, I. Tubbe, P. R. Galle et al., “Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27,” Journal of Experimental Medicine, vol. 203, no. 8, pp. 1875–1881, 2006. View at Publisher · View at Google Scholar · View at Scopus
  81. G. Perona-Wright, J. E. Kohlmeier, E. Bassity et al., “Persistent loss of IL-27 responsiveness in CD8+ memory T cells abrogates IL-10 expression in a recall response,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 45, pp. 18535–18540, 2012. View at Publisher · View at Google Scholar · View at Scopus
  82. F. Larousserie, P. Charlot, E. Bardel, J. Froger, R. A. Kastelein, and O. Devergne, “Differential effects of IL-27 on human B cell subsets,” Journal of Immunology, vol. 176, no. 10, pp. 5890–5897, 2006. View at Publisher · View at Google Scholar · View at Scopus
  83. Z. Dong, W. Tai, W. Lei, Y. Wang, Z. Li, and T. Zhang, “IL-27 inhibits the TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells,” BMC Cell Biology, vol. 17, no. 1, article 7, 2016. View at Publisher · View at Google Scholar · View at Scopus
  84. J. Diegelmann, T. Olszak, B. Göke, R. S. Blumberg, and S. Brand, “A novel role for interleukin-27 (IL-27) as mediator of intestinal epithelial barrier protection mediated via differential signal transducer and activator of transcription (STAT) protein signaling and induction of antibacterial and anti-inflammatory proteins,” Journal of Biological Chemistry, vol. 287, no. 1, pp. 286–298, 2012. View at Publisher · View at Google Scholar · View at Scopus
  85. S. Aparicio-Siegmund and C. Garbers, “The biology of interleukin-27 reveals unique pro- and anti-inflammatory functions in immunity,” Cytokine and Growth Factor Reviews, vol. 26, no. 5, pp. 579–586, 2015. View at Publisher · View at Google Scholar · View at Scopus
  86. S. Lucas, N. Ghilardi, J. Li, and F. J. De Sauvage, “IL-27 regulates IL-12 responsiveness of naïve CD4+ T cells through Stat1-dependent and -independent mechanisms,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 25, pp. 15047–15052, 2003. View at Publisher · View at Google Scholar · View at Scopus
  87. A. Takeda, S. Hamano, A. Yamanaka et al., “Cutting edge: role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment,” Journal of Immunology, vol. 170, no. 10, pp. 4886–4890, 2003. View at Publisher · View at Google Scholar · View at Scopus
  88. N. Morishima, T. Owaki, M. Asakawa, S. Kamiya, J. Mizuguchi, and T. Yoshimoto, “Augmentation of effector CD8+ T cell generation with enhanced granzyme B expression by IL-27,” Journal of Immunology, vol. 175, no. 3, pp. 1686–1693, 2005. View at Publisher · View at Google Scholar · View at Scopus
  89. K. D. Mayer, K. Mohrs, W. Reiley et al., “Cutting edge: T-bet and IL-27R are critical for in vivo IFN-γ production by CD8 T cells during infection,” The Journal of Immunology, vol. 180, no. 2, pp. 693–697, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. R. Schneider, T. Yaneva, D. Beauseigle, L. El-Khoury, and N. Arbour, “IL-27 increases the proliferation and effector functions of human naïve CD8+ T lymphocytes and promotes their development into Tc1 cells,” European Journal of Immunology, vol. 41, no. 1, pp. 47–59, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. M. Batten, N. M. Kljavin, J. Li, M. J. Walter, F. J. De Sauvage, and N. Ghilardi, “Cutting edge: IL-27 is a potent inducer of IL-10 but not FoxP3 in murine T cells,” Journal of Immunology, vol. 180, no. 5, pp. 2752–2756, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. Z. Liu, J.-Q. Liu, F. Talebian, L.-C. Wu, S. Li, and X.-F. Bai, “IL-27 enhances the survival of tumor antigen-specific CD8+ T cells and programs them into IL-10-producing, memory precursor-like effector cells,” European Journal of Immunology, vol. 43, no. 2, pp. 468–479, 2013. View at Publisher · View at Google Scholar · View at Scopus
  93. D. Artis, A. Villarino, M. Silverman et al., “The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of type 2 immunity,” The Journal of Immunology, vol. 173, no. 9, pp. 5626–5634, 2004. View at Publisher · View at Google Scholar · View at Scopus
  94. Y. Miyazaki, H. Inoue, M. Matsumura et al., “Exacerbation of experimental allergic asthma by augmented Th2 responses in WSX-1-deficient mice,” Journal of Immunology, vol. 175, no. 4, pp. 2401–2407, 2005. View at Publisher · View at Google Scholar · View at Scopus
  95. T. Yoshimoto, T. Yoshimoto, K. Yasuda, J. Mizuguchi, and K. Nakanishi, “IL-27 suppresses Th2 cell development and Th2 cytokines production from polarized Th2 cells: a novel therapeutic way for Th2-mediated allergic inflammation,” The Journal of Immunology, vol. 179, no. 7, pp. 4415–4423, 2007. View at Publisher · View at Google Scholar · View at Scopus
  96. M. Xie, A. T. Mustovich, Y. Jiang et al., “IL-27 and type 2 immunity in asthmatic patients: association with severity, CXCL9, and signal transducer and activator of transcription signaling,” Journal of Allergy and Clinical Immunology, vol. 135, no. 2, pp. 386–394, 2015. View at Publisher · View at Google Scholar · View at Scopus
  97. C. Pot, L. Apetoh, A. Awasthi, and V. K. Kuchroo, “Induction of regulatory Tr1 cells and inhibition of TH17 cells by IL-27,” Seminars in Immunology, vol. 23, no. 6, pp. 438–445, 2011. View at Publisher · View at Google Scholar · View at Scopus
  98. R. R. Meka, S. H. Venkatesha, S. Dudics, B. Acharya, and K. D. Moudgil, “IL-27-induced modulation of autoimmunity and its therapeutic potential,” Autoimmunity Reviews, vol. 14, no. 12, pp. 1131–1141, 2015. View at Publisher · View at Google Scholar · View at Scopus
  99. J. S. Stumhofer, A. Laurence, E. H. Wilson et al., “Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system,” Nature Immunology, vol. 7, no. 9, pp. 937–945, 2006. View at Publisher · View at Google Scholar · View at Scopus
  100. C. Diveu, M. J. McGeachy, K. Boniface et al., “IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells,” Journal of Immunology, vol. 182, no. 9, pp. 5748–5756, 2009. View at Publisher · View at Google Scholar · View at Scopus
  101. A. Awasthi, Y. Carrier, J. P. S. Peron et al., “A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells,” Nature Immunology, vol. 8, no. 12, pp. 1380–1389, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. J. S. Stumhofer, J. S. Silver, A. Laurence et al., “Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10,” Nature Immunology, vol. 8, no. 12, pp. 1363–1371, 2007. View at Publisher · View at Google Scholar · View at Scopus
  103. D. C. Fitzgerald, G.-X. Zhang, M. El-Behi et al., “Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells,” Nature Immunology, vol. 8, no. 12, pp. 1372–1379, 2007. View at Publisher · View at Google Scholar · View at Scopus
  104. N. Chihara, A. Madi, K. Karwacz, A. Awasthi, and V. K. Kuchroo, “Differentiation and characterization of Tr1 cells,” in Current Protocols in Immunology, vol. 113, pp. 3.27.1–3.27.10, John Wiley & Sons, 2016. View at Google Scholar
  105. C. Pot, H. Jin, A. Awasthi et al., “Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells,” The Journal of Immunology, vol. 183, no. 2, pp. 797–801, 2009. View at Publisher · View at Google Scholar · View at Scopus
  106. T. Owaki, M. Asakawa, S. Kamiya et al., “IL-27 suppresses CD28-mediated [correction of medicated] IL-2 production through suppressor of cytokine signaling 3,” Journal of Immunology, vol. 176, no. 5, pp. 2773–2780, 2006. View at Google Scholar
  107. A. V. Villarino, J. S. Stumhofer, C. J. M. Saris, R. A. Kastelein, F. J. De Sauvage, and C. A. Hunter, “IL-27 limits IL-2 production during Th1 differentiation,” Journal of Immunology, vol. 176, no. 1, pp. 237–247, 2006. View at Publisher · View at Google Scholar · View at Scopus
  108. K. Hirahara, K. Ghoreschi, X.-P. Yang et al., “Interleukin-27 priming of T cells controls IL-17 production in trans via induction of the ligand PD-L1,” Immunity, vol. 36, no. 6, pp. 1017–1030, 2012. View at Publisher · View at Google Scholar · View at Scopus
  109. S. Karakhanova, T. Bedke, A. H. Enk, and K. Mahnke, “Il-27 renders DC immunosuppressive by induction of B7-H1,” Journal of Leukocyte Biology, vol. 89, no. 6, pp. 837–845, 2011. View at Publisher · View at Google Scholar · View at Scopus
  110. B. M. Matta, G. Raimondi, B. R. Rosborough, T. L. Sumpter, and A. W. Thomson, “IL-27 production and STAT3-dependent upregulation of B7-H1 mediate immune regulatory functions of liver plasmacytoid dendritic cells,” Journal of Immunology, vol. 188, no. 11, pp. 5227–5237, 2012. View at Publisher · View at Google Scholar · View at Scopus
  111. I. D. Mascanfroni, A. Yeste, S. M. Vieira et al., “IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39,” Nature Immunology, vol. 14, no. 10, pp. 1054–1063, 2013. View at Publisher · View at Google Scholar · View at Scopus
  112. J.-Y. Jung, M. Gleave Parson, J. D. Kraft et al., “Elevated interleukin-27 levels in human neonatal macrophages regulate indoleamine dioxygenase in a STAT-1 and STAT-3-dependent manner,” Immunology, vol. 149, no. 1, pp. 35–47, 2016. View at Publisher · View at Google Scholar · View at Scopus
  113. S. Kamiya, T. Owaki, N. Morishima, F. Fukai, J. Mizuguchi, and T. Yoshimoto, “An indispensable role for STAT1 in IL-27-induced T-bet expression but not proliferation of naive CD4+ T cells,” Journal of Immunology, vol. 173, no. 6, pp. 3871–3877, 2004. View at Publisher · View at Google Scholar · View at Scopus
  114. T. Yoshimoto, K. Okada, N. Morishima et al., “Induction of IgG2a class switching in B cells by IL-27,” Journal of Immunology, vol. 173, no. 4, pp. 2479–2485, 2004. View at Publisher · View at Google Scholar · View at Scopus
  115. K. Moro, H. Kabata, M. Tanabe et al., “Interferon and IL-27 antagonize the function of group 2 innate lymphoid cells and type 2 innate immune responses,” Nature Immunology, vol. 17, no. 1, pp. 76–86, 2016. View at Publisher · View at Google Scholar · View at Scopus
  116. C. U. Duerr, C. D. A. McCarthy, B. C. Mindt et al., “Type I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells,” Nature Immunology, vol. 17, no. 1, pp. 65–75, 2016. View at Publisher · View at Google Scholar · View at Scopus
  117. X. M. Feng, N. Liu, S. G. Yang et al., “Regulation of the class II and class I MHC pathways in human THP-1 monocytic cells by interleukin-27,” Biochemical and Biophysical Research Communications, vol. 367, no. 3, pp. 553–559, 2008. View at Publisher · View at Google Scholar · View at Scopus
  118. X. M. Feng, X. L. Chen, N. Liu et al., “Interleukin-27 upregulates major histocompatibility complex class II expression in primary human endothelial cells through induction of major histocompatibility complex class II transactivator,” Human Immunology, vol. 68, no. 12, pp. 965–972, 2007. View at Publisher · View at Google Scholar · View at Scopus
  119. H. Bender, M. Y. Wiesinger, C. Nordhoff et al., “Interleukin-27 displays interferon-γ-like functions in human hepatoma cells and hepatocytes,” Hepatology, vol. 50, no. 2, pp. 585–591, 2009. View at Publisher · View at Google Scholar · View at Scopus
  120. C. Schoenherr, R. Weiskirchen, and S. Haan, “Interleukin-27 acts on hepatic stellate cells and induces signal transducer and activator of transcription 1-dependent responses,” Cell Communication and Signaling, vol. 8, article no. 19, 2010. View at Publisher · View at Google Scholar · View at Scopus
  121. J.-Y. Jung, L. L. Roberts, and C. M. Robinson, “The presence of interleukin-27 during monocyte-derived dendritic cell differentiation promotes improved antigen processing and stimulation of T cells,” Immunology, vol. 144, no. 4, pp. 649–660, 2015. View at Publisher · View at Google Scholar · View at Scopus
  122. J. M. Fakruddin, R. A. Lempicki, R. J. Gorelick et al., “Noninfectious papilloma virus-like particles inhibit HIV-1 replication: implications for immune control of HIV-1 infection by IL-27,” Blood, vol. 109, no. 5, pp. 1841–1849, 2007. View at Publisher · View at Google Scholar · View at Scopus
  123. T. Imamichi, J. Yang, D.-W. Huang et al., “IL-27, a novel anti-HIV cytokine, activates multiple interferon-inducible genes in macrophages,” AIDS, vol. 22, no. 1, pp. 39–45, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. C. Guzzo, M. Jung, A. Graveline, B. W. Banfield, and K. Gee, “IL-27 increases BST-2 expression in human monocytes and T cells independently of type I IFN,” Scientific Reports, vol. 2, article no. 974, 2012. View at Publisher · View at Google Scholar · View at Scopus
  125. T. Imamichi, J. Yang, D. W. Huang, B. Sherman, and R. A. Lempicki, “Interleukin-27 induces interferon-inducible genes: analysis of gene expression profiles using affymetrix microarray and DAVID,” Methods in Molecular Biology, vol. 820, pp. 25–53, 2012. View at Publisher · View at Google Scholar · View at Scopus
  126. A. C. Frank, X. Zhang, A. Katsounas, J. P. Bharucha, S. Kottilil, and T. Imamichi, “Interleukin-27, an anti-HIV-1 cytokine, inhibits replication of hepatitis C virus,” Journal of Interferon and Cytokine Research, vol. 30, no. 6, pp. 427–431, 2010. View at Publisher · View at Google Scholar · View at Scopus
  127. M. Wittmann, R. Doble, M. Bachmann, J. Pfeilschifter, T. Werfel, and H. Mühl, “IL-27 regulates IL-18 binding protein in skin resident cells,” PLoS ONE, vol. 7, no. 6, Article ID e38751, 2012. View at Publisher · View at Google Scholar · View at Scopus
  128. M. V. Corrias, M. Occhino, M. Croce et al., “Lack of HLA-class I antigens in human neuroblastoma cells: analysis of its relationship to TAP and tapasin expression,” Tissue Antigens, vol. 57, no. 2, pp. 110–117, 2001. View at Publisher · View at Google Scholar · View at Scopus
  129. C. Rolvering, A. D. Zimmer, I. Kozar et al., “Crosstalk between different family members: IL27 recapitulates IFNγ responses in HCC cells, but is inhibited by IL6-type cytokines,” Biochimica et Biophysica Acta, vol. 1864, no. 3, pp. 516–526, 2017. View at Publisher · View at Google Scholar
  130. M. Duan, Z. Ning, Z. Fu et al., “Decreased IL-27 negatively correlated with Th17 cells in non-small-cell lung cancer patients,” Mediators of Inflammation, vol. 2015, Article ID 802939, 8 pages, 2015. View at Publisher · View at Google Scholar · View at Scopus
  131. M. E. Turnis, D. V. Sawant, A. L. Szymczak-Workman et al., “Interleukin-35 limits anti-tumor immunity,” Immunity, vol. 44, no. 2, pp. 316–329, 2016. View at Publisher · View at Google Scholar · View at Scopus
  132. D. Diakowska, A. Lewandowski, K. Markocka-Maczka, and K. Grabowski, “Concentration of serum interleukin-27 increase in patients with lymph node metastatic gastroesophageal cancer,” Advances in Clinical and Experimental Medicine, vol. 22, no. 5, pp. 683–691, 2013. View at Google Scholar · View at Scopus
  133. D. Lu, X. Zhou, L. Yao, C. Liu, F. Jin, and Y. Wu, “Clinical implications of the interleukin 27 serum level in breast cancer,” Journal of Investigative Medicine, vol. 62, no. 3, pp. 627–631, 2014. View at Publisher · View at Google Scholar · View at Scopus
  134. S. Di Meo, I. Airoldi, C. Sorrentino, A. Zorzoli, S. Esposito, and E. Di Carlo, “Interleukin-30 expression in prostate cancer and its draining lymph nodes correlates with advanced grade and stage,” Clinical Cancer Research, vol. 20, no. 3, pp. 585–594, 2014. View at Publisher · View at Google Scholar · View at Scopus
  135. I. Airoldi, C. Cocco, C. Sorrentino et al., “Interleukin-30 promotes breast cancer growth and progression,” Cancer Research, vol. 76, no. 21, pp. 6218–6229, 2016. View at Publisher · View at Google Scholar
  136. J. Gonin, A. Carlotti, C. Dietrich et al., “Expression of IL-27 by tumor cells in invasive cutaneous and metastatic melanomas,” PLoS ONE, vol. 8, no. 10, Article ID e75694, 2013. View at Publisher · View at Google Scholar
  137. F. Larousserie, E. Bardel, A. Coulomb L'Herminé et al., “Variable expression of Epstein-Barr virus-induced gene 3 during normal B-cell differentiation and among B-cell lymphomas,” Journal of Pathology, vol. 209, no. 3, pp. 360–368, 2006. View at Publisher · View at Google Scholar · View at Scopus
  138. M. L. Hanson, J. A. Hixon, W. Li et al., “Oral delivery of IL-27 recombinant bacteria attenuates immune colitis in mice,” Gastroenterology, vol. 146, no. 1, pp. 210–221.e13, 2014. View at Publisher · View at Google Scholar · View at Scopus
  139. W. Niedbala, B. Cai, X. Wei et al., “Interleukin 27 attenuates collagen-induced arthritis,” Annals of the Rheumatic Diseases, vol. 67, no. 10, pp. 1474–1479, 2008. View at Publisher · View at Google Scholar · View at Scopus
  140. C. Andrews, M. H. McLean, and S. K. Durum, “Interleukin-27 as a novel therapy for inflammatory bowel disease: a critical review of the literature,” Inflammatory Bowel Diseases, vol. 22, no. 9, pp. 2255–2264, 2016. View at Publisher · View at Google Scholar · View at Scopus
  141. F. Larousserie, S. Pflanz, A. Coulomb-L'Herminé, N. Brousse, R. Kastelein, and O. Devergne, “Expression of IL-27 in human Th1-associated granulomatous diseases,” The Journal of Pathology, vol. 202, no. 2, pp. 164–171, 2004. View at Publisher · View at Google Scholar · View at Scopus