Table of Contents Author Guidelines Submit a Manuscript
Clinical and Developmental Immunology
Volume 2012, Article ID 931952, 19 pages
http://dx.doi.org/10.1155/2012/931952
Review Article

Exploiting the Interplay between Innate and Adaptive Immunity to Improve Immunotherapeutic Strategies for Epstein-Barr-Virus-Driven Disorders

1Cancer Bioimmunotherapy Unit CRO-IRCCS, National Cancer Institute, Via F. Gallini 2, 33081 Aviano, Italy
2Department of Oncology and Surgical Sciences, University of Padova, Via F. Gallini 2, 35128 Padova, Italy
3Cancer Bioimmunotherapy Unit, Department of Medical Oncology, CRO National Cancer Institute, Via F. Gallini 2, 33081 Aviano, Italy

Received 27 July 2011; Revised 28 September 2011; Accepted 16 October 2011

Academic Editor: Mauro Tognon

Copyright © 2012 Debora Martorelli 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. P. M. Arlen, “Prostate cancer immunotherapy: the role for sipuleucel-T and other immunologic approaches,” Oncology, vol. 25, no. 3, pp. 261–262, 2011. View at Google Scholar
  2. K. Palucka, H. Ueno, and J. Banchereau, “Recent developments in cancer vaccines,” Journal of Immunology, vol. 186, no. 3, pp. 1325–1331, 2011. View at Publisher · View at Google Scholar
  3. R. Madan and J. Gulley, “The current and emerging role of immunotherapy in prostate cancer,” Clinical Genitourinary Cancer, vol. 8, no. 1, pp. 10–16, 2010. View at Publisher · View at Google Scholar
  4. S. Cecco, E. Muraro, E. Giacomin et al., “Cancer vaccines in phase II/III clinical trials: state of the art and future perspectives,” Current Cancer Drug Targets, vol. 11, no. 1, pp. 85–102, 2011. View at Publisher · View at Google Scholar
  5. V. Vonka, “Immunotherapy of chronic myeloid leukemia: present state and future prospects,” Immunotherapy, vol. 2, no. 2, pp. 227–241, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. M. J. Besser, L. Hershkovitz, J. Schachter, and A. J. Treves, “Focus on adoptive T cell transfer trials in melanoma,” Clinical and Developmental Immunology, vol. 2010, pp. 260–267, 2010. View at Publisher · View at Google Scholar
  7. S. C. Goldstein and D. L. Porter, “Allogeneic immunotherapy to optimize the graft-versus-tumor effect: concepts and controversies,” Expert Review of Hematology, vol. 3, no. 3, pp. 301–314, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. K. K. Jain, “Personalized cancer vaccines,” Expert Opinion on Biological Therapy, vol. 10, no. 12, pp. 1637–1647, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. F. Chen, J. Z. Zou, L. Di Renzo et al., “A subpopulation of normal B cells latently infected with Epstein-Barr virus resembles Burkitt lymphoma cells in expressing EBNA-1 but not EBNA-2 or LMP1,” Journal of Virology, vol. 69, no. 6, pp. 3752–3758, 1995. View at Google Scholar · View at Scopus
  10. G. J. Babcock, D. Hochberg, and D. A. Thorley-Lawson, “The expression pattern of Epstein-Barr virus latent genes in vivo is dependent upon the differentiation stage of the infected B cell,” Immunity, vol. 13, no. 4, pp. 497–506, 2000. View at Google Scholar · View at Scopus
  11. R. Dolcetti and M. G. Masucci, “Epstein-Barr virus: induction and control of cell transformation,” Journal of Cellular Physiology, vol. 196, no. 2, pp. 207–218, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. M. R. Lerner, N. C. Andrews, G. Miller, and J. A. Steitz, “Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 78, no. 2, pp. 805–809, 1981. View at Google Scholar · View at Scopus
  13. C. H. Lecellier, P. Dunoyer, K. Arar et al., “A cellular microRNA mediates antiviral defense in human cells,” Science, vol. 308, no. 5721, pp. 557–560, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Pfeffer, M. Zavolan, F. A. Grasser et al., “Identification of virus-encoded microRNAs,” Science, vol. 304, no. 5671, pp. 734–736, 2004. View at Publisher · View at Google Scholar · View at Scopus
  15. C. S. Sullivan, A. T. Grundhoff, S. Tevethia, J. M. Pipas, and D. Ganem, “SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells,” Nature, vol. 435, no. 7042, pp. 682–686, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. D. P. Bartel, “MicroRNAs: genomics, biogenesis, mechanism, and function,” Cell, vol. 116, no. 2, pp. 281–297, 2004. View at Publisher · View at Google Scholar · View at Scopus
  17. V. Ambros, “The functions of animal microRNAs,” Nature, vol. 431, no. 7006, pp. 350–355, 2004. View at Publisher · View at Google Scholar · View at Scopus
  18. J. S. Mattick and I. V. Makunin, “Small regulatory RNAs in mammals,” Human Molecular Genetics, vol. 14, no. 1, pp. R121–R132, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. P. Xu, M. Guo, and B. A. Hay, “MicroRNAs and the regulation of cell death,” Trends in Genetics, vol. 20, no. 12, pp. 617–624, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. A. Esquela-Kerscher and F. J. Slack, “Oncomirs—microRNAs with a role in cancer,” Nature Reviews Cancer, vol. 6, no. 4, pp. 259–269, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. J. Kluiver, S. Poppema, D. De Jong et al., “BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas,” Journal of Pathology, vol. 207, no. 2, pp. 243–249, 2005. View at Publisher · View at Google Scholar · View at Scopus
  22. S. A. Connolly, J. O. Jackson, T. S. Jardetzky, and R. Longnecker, “Fusing structure and function: a structural view of the herpesvirus entry machinery,” Nature Reviews Microbiology, vol. 9, no. 5, pp. 369–381, 2011. View at Publisher · View at Google Scholar
  23. A.B. Rickinson and E.D. Kieff, “Epstein-Barr virus,” in Field Virology, pp. 2655–700, Lippincott Williams & Wilkins, Philadelphia, Pa, USA, 5th edition, 2007. View at Google Scholar
  24. K. Gatter and G. Desol, The Diagnosis of Lymphoproliferative Diseases: An Atlas, Oxford University Press, Oxford, UK, 2002.
  25. A. Carbone and A. Gloghini, “AIDS-related lymphomas: from pathogenesis to pathology,” The British Journal of Haematology, vol. 130, no. 5, pp. 662–670, 2005. View at Publisher · View at Google Scholar · View at Scopus
  26. A. A. Brink, D. F. Dukers, A. J. C. van den Brule et al., “Presence of Epstein-Barr virus latency type III at the single cell level in post-transplantation lymphoproliferative disorders and AIDS related lymphomas,” Journal of Clinical Pathology, vol. 50, no. 11, pp. 911–918, 1997. View at Google Scholar · View at Scopus
  27. P. J. Pickhardt and M. J. Siegel, “Posttransplantation lymphoproliferative disorder of the abdomen: CT evaluation in 51 patients,” Radiology, vol. 213, no. 1, pp. 73–78, 1999. View at Google Scholar · View at Scopus
  28. Q. Tao, L. S. Young, C. B. J. Woodman, and P. G. Murray, “Epstein-Barr virus (EBV) and its associated human cancers—genetics, epigenetics, pathobiology and novel therapeutics,” Frontiers in Bioscience, vol. 11, no. 2, pp. 2672–2713, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Keay, D. Oldach, A. Wiland et al., “Posttransplantation lymphoproliferative disorder associated with OKT3 and decreased antiviral prophylaxis in pancreas transplant recipients,” Clinical Infectious Diseases, vol. 26, no. 3, pp. 596–600, 1998. View at Google Scholar · View at Scopus
  30. R. Purighalla, R. Shapiro, M. L. Jordan et al., “Acute renal allograft rejection in patients with Epstein-Barr virus associated post-transplant lymphoproliferative disorder,” Clinical Transplantation, vol. 11, no. 6, pp. 574–576, 1997. View at Google Scholar · View at Scopus
  31. S. A. Birkeland, H. K. Andersen, and S. J. Hamilton-Dutoit, “Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol,” Transplantation, vol. 67, no. 9, pp. 1209–1214, 1999. View at Publisher · View at Google Scholar · View at Scopus
  32. M. Hummel, I. Anagnostopoulos, P. Korbjuhn, and H. Stein, “Epstein-Barr virus in B-cell non-Hodgkin's lymphomas: unexpected infection patterns and different infection incidence in low- and high-grade types,” Journal of Pathology, vol. 175, no. 3, pp. 263–271, 1995. View at Publisher · View at Google Scholar · View at Scopus
  33. B.E. Griffin and R. Rochford, Endemic Burkitt's Lymphoma, Caister Academic Press, Norfolk, UK, 2005.
  34. L. S. Young and A. B. Rickinson, “Epstein-Barr virus: 40 years on,” Nature Reviews Cancer, vol. 4, no. 10, pp. 757–768, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. R. Küppers, “B cells under influence: transformation of B cells by Epstein-Barr virus,” Nature Reviews Immunology, vol. 3, no. 10, pp. 801–812, 2003. View at Google Scholar · View at Scopus
  36. G. L. Kelly, A. E. Milner, G. S. Baldwin, A. I. Bell, and A. B. Rickinson, “Three restricted forms of Epstein-Barr virus latency counteracting apoptosis in c-myc-expressing Burkitt lymphoma cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 40, pp. 14935–14940, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. J. B. Wilson, J. L. Bell, and A. J. Levine, “Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in transgenic mice,” EMBO Journal, vol. 15, no. 12, pp. 3117–3126, 1996. View at Google Scholar · View at Scopus
  38. N. Kitagawa, M. Goto, K. Kurozumi et al., “Epstein-Barr virus-encoded poly(A)- RNA supports Burkitt's lymphoma growth through interleukin-10 induction,” EMBO Journal, vol. 19, no. 24, pp. 6742–6750, 2000. View at Publisher · View at Google Scholar · View at Scopus
  39. R. Kuppers and R. Dalla-Favera, “Mechanisms of chromosomal translocations in B cell lymphomas,” Oncogene, vol. 20, no. 40, pp. 5580–5594, 2001. View at Publisher · View at Google Scholar · View at Scopus
  40. M. T. Hemann, A. Bric, J. Teruya-Feldstein et al., “Evasion of the p53 tumour surveillance network by tumour-derived MYC mutants,” Nature, vol. 436, no. 7052, pp. 807–811, 2005. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Egle, A. W. Harris, P. Bouillet, and S. Cory, “Bim is a suppressor of Myc-induced mouse B cell leukemia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 16, pp. 6164–6169, 2004. View at Publisher · View at Google Scholar · View at Scopus
  42. K. N. Heller, F. Arrey, P. Steinherz et al., “Patients with Epstein Barr virus-positive lymphomas have decreased CD4 + T-cell responses to the viral nuclear antigen 1,” International Journal of Cancer, vol. 123, no. 12, pp. 2824–2831, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. J. L. Kutok and F. Wang, “Spectrum of Epstein-Barr virus-associated diseases,” Annual Review of Pathology, vol. 1, pp. 375–404, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. H. Herbst, H. D. Foss, J. Samol et al., “Frequent expression of interleukin-10 by Epstein-Barr virus-harboring tumor cells of Hodgkin's disease,” Blood, vol. 87, no. 7, pp. 2918–2929, 1996. View at Google Scholar · View at Scopus
  45. S. M. Hsu, J. Lin, S. S. Xie, P. L. Hsu, and S. Rich, “Abundant expression of transforming growth factor-β1 and -β2 by Hodgkin's Reed-Sternberg cells and by reactive T lymphocytes in Hodgkin's disease,” Human Pathology, vol. 24, no. 3, pp. 249–255, 1993. View at Publisher · View at Google Scholar · View at Scopus
  46. N. A. Marshall, L. E. Christie, L. R. Munro et al., “Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma,” Blood, vol. 103, no. 5, pp. 1755–1762, 2004. View at Publisher · View at Google Scholar · View at Scopus
  47. D. A. Al-Hakeem, S. Fedele, R. Carlos, and S. Porter, “Extranodal NK/T-cell lymphoma, nasal type,” Oral Oncology, vol. 43, no. 1, pp. 4–14, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. S. Swerdlow, E. Campo, N. Harris, E. Jaffe, and S. H. S. Pileri, WHO classification of Tumors of the Hematopoietic and Lymphoid Tissues, International Agency of Research on Cancer (IARC), 2008.
  49. P. Kanavaros, M. C. Lescs, J. Briere et al., “Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus,” Blood, vol. 81, no. 10, pp. 2688–2695, 1993. View at Google Scholar · View at Scopus
  50. A. Jaccard, N. Gachard, and B. Marin, “Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study,” Blood, vol. 117, no. 6, pp. 1834–1839, 2011. View at Google Scholar
  51. J. R. Anderson, J. O. Armitage, and D. D. Weisenburger, “Epidemiology of the non-Hodgkin's lymphomas: distributions of the major subtypes differ by geographic locations. Non-Hodgkin's Lymphoma Classification Project,” Annals of Oncology, vol. 9, no. 7, pp. 717–720, 1998. View at Google Scholar
  52. W. Cheuk, J. K. C. Chan, T. W. Shek et al., “Inflammatory pseudotumor-like follicular dendritic cell tumor: a distinctive low-grade malignant intra-abdominal neoplasm with consistent epstein—Barr virus association,” The American Journal of Surgical Pathology, vol. 25, no. 6, pp. 721–731, 2001. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Andersson-Anvret, N. Forsby, G. Klein, and W. Henle, “Relationship between the Epstein-Barr virus and undifferentiated nasopharyngeal carcinoma: correlated nucleic acid hybridization and histopathological examination,” International Journal of Cancer, vol. 20, no. 4, pp. 486–494, 1977. View at Google Scholar · View at Scopus
  54. C. M. Borza and L. M. Hutt-Fletcher, “Alternate replication in B cells and epithelial cells switches tropism of Epstein-Barr virus,” Nature Medicine, vol. 8, no. 6, pp. 594–599, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. E. M. Miyashita, B. Yang, G. J. Babcock, and D. A. Thorley-Lawson, “Identification of the site of Epstein-Barr virus persistence in vivo as a resting B cell,” Journal of Virology, vol. 71, no. 7, pp. 4882–4891, 1997. View at Google Scholar · View at Scopus
  56. J. W. Sixbey, J. G. Nedrud, and N. Raab Traub, “Epstein-Barr virus replication in oropharyngeal epithelial cells,” The New England Journal of Medicine, vol. 310, no. 19, pp. 1225–1230, 1984. View at Google Scholar · View at Scopus
  57. R. Kobayashi, H. Takeuchi, M. Sasaki, M. Hasegawa, and K. Hirai, “Detection of Epstein-Barr virus infection in the epithelial cells and lymphocytes of non-neoplastic tonsils by in situ hybridization and in situ PCR,” Archives of Virology, vol. 143, no. 4, pp. 803–813, 1998. View at Publisher · View at Google Scholar · View at Scopus
  58. I. Anagnostopoulos, M. Hummel, C. Kreschel, and H. Stein, “Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus,” Blood, vol. 85, no. 3, pp. 744–750, 1995. View at Google Scholar · View at Scopus
  59. G. Niedobitek, A. Agathanggelou, N. Steven, and L. S. Young, “Epstein-Barr virus (EBV) in infectious mononucleosis: detection of the virus in tonsillar B lymphocytes but not in desquamated oropharyngeal epithelial cells,” Journal of Clinical Pathology—Molecular Pathology, vol. 53, no. 1, pp. 37–42, 2000. View at Publisher · View at Google Scholar · View at Scopus
  60. S. D. Hudnall, Y. Ge, L. Wei, N. P. Yang, H. Q. Wang, and T. Chen, “Distribution and phenotype of Epstein-Barr virus-infected cells in human pharyngeal tonsils,” Modern Pathology, vol. 18, no. 4, pp. 519–527, 2005. View at Publisher · View at Google Scholar · View at Scopus
  61. D. K. Paramita, C. Fatmawati, H. Juwana et al., “Humoral immune responses to Epstein-Barr virus encoded tumor associated proteins and their putative extracellular domains in nasopharyngeal carcinoma patients and regional controls,” Journal of Medical Virology, vol. 83, no. 4, pp. 665–678, 2011. View at Publisher · View at Google Scholar
  62. M. Y. Liu, Y. T. Huang, T. S. Sheen, J. Y. Chen, and C. H. Tsai, “Immune responses to Epstein-Barr virus lytic proteins in patients with nasopharyngeal carcinoma,” Journal of Medical Virology, vol. 73, no. 4, pp. 574–582, 2004. View at Publisher · View at Google Scholar · View at Scopus
  63. G. Henle and W. Henle, “Epstein Barr virus specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma,” International Journal of Cancer, vol. 17, no. 1, pp. 1–7, 1976. View at Google Scholar · View at Scopus
  64. A. D. Hislop, N. E. Annels, N. H. Gudgeon, A. M. Leese, and A. B. Rickinson, “Epitope-specific evolution of human CD8(+) T cell responses from primary to persistent phases of Epstein-Barr virus infection,” Journal of Experimental Medicine, vol. 195, no. 7, pp. 893–905, 2002. View at Publisher · View at Google Scholar · View at Scopus
  65. X. Lin, N. H. Gudgeon, E. P. Hui et al., “CD4 and CD8 T cell responses to tumour-associated Epstein-Barr virus antigens in nasopharyngeal carcinoma patients,” Cancer Immunology, Immunotherapy, vol. 57, no. 7, pp. 963–975, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. J. Li, X. H. Zeng, H. Y. Mo et al., “Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy,” PLoS One, vol. 2, no. 11, Article ID e1122, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. P. Comoli, P. Pedrazzoli, R. Maccario et al., “Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein-Barr virus-targeted cytotoxic T lymphocytes,” Journal of Clinical Oncology, vol. 23, no. 35, pp. 8942–8949, 2005. View at Publisher · View at Google Scholar · View at Scopus
  68. K. M. Lau, S. H. Cheng, K. W. Lo et al., “Increase in circulating Foxp3 + CD4 + CD25(high) regulatory T cells in nasopharyngeal carcinoma patients,” The British Journal of Cancer, vol. 96, no. 4, pp. 617–622, 2007. View at Publisher · View at Google Scholar · View at Scopus
  69. J. Klibi, T. Niki, A. Riedel et al., “Blood diffusion and Th1-suppressive effects of galectin-9-containing exosomes released by Epstein-Barr virus-infected nasopharyngeal carcinoma cells,” Blood, vol. 113, no. 9, pp. 1957–1966, 2009. View at Publisher · View at Google Scholar · View at Scopus
  70. M. Yao, K. Ohshima, J. Suzumiya, T. Kume, T. O. Shiroshita, and M. Kikuchi, “Interleukin-10 expression and cytotoxic-T-cell response in Epstein-Barr-virus-associated nasopharyngeal carcinoma,” International Journal of Cancer, vol. 72, no. 3, pp. 398–402, 1997. View at Publisher · View at Google Scholar · View at Scopus
  71. A. Beck, D. Pzolt, G. G. Grabenbauer et al., “Expression of cytokine and chemokine genes in Epstein-Barr virus-associated nasopharyngeal carcinoma: comparison with Hodgkin's disease,” Journal of Pathology, vol. 194, no. 2, pp. 145–151, 2001. View at Publisher · View at Google Scholar · View at Scopus
  72. R. Khanna, P. Busson, S. R. Burrows et al., “Molecular characterization of antigen-processing function in nasopharyngeal carcinoma (NPC): evidence for efficient presentation of Epstein-Barr virus cytotoxic T-cell epitopes by NPC cells,” Cancer Research, vol. 58, no. 2, pp. 310–314, 1998. View at Google Scholar · View at Scopus
  73. T. Ogino, S. Moriai, Y. Ishida et al., “Association of immunoescape mechanisms with Epstein-Barr virus infection in nasopharyngeal carcinoma,” International Journal of Cancer, vol. 120, no. 11, pp. 2401–2410, 2007. View at Publisher · View at Google Scholar · View at Scopus
  74. S. M. Krams and O. M. Martinez, “Epstein-Barr virus, rapamycin, and host immune responses,” Current Opinion in Organ Transplantation, vol. 13, no. 6, pp. 563–568, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. F. Pietersma, E. Piriou, and D. van Baarle, “Immune surveillance of EBV-infected B cells and the development of non-Hodgkin lymphomas in immunocompromised patients,” Leukemia and Lymphoma, vol. 49, no. 6, pp. 1028–1041, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. D. Iwakiri and K. Takada, “Role of EBERs in the pathogenesis of EBV infection,” Advances in Cancer Research, vol. 107, pp. 119–136, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. M. Savard and J. Gosselin, “Epstein-Barr virus immunossuppression of innate immunity mediated by phagocytes,” Virus Research, vol. 119, no. 2, pp. 134–145, 2006. View at Publisher · View at Google Scholar · View at Scopus
  78. V. Levitsky and M. G. Masucci, “Manipulation of immune responses by Epstein-Barr virus,” Virus Research, vol. 88, no. 1-2, pp. 71–86, 2002. View at Publisher · View at Google Scholar · View at Scopus
  79. I. Fathallah, P. Parroche, H. Gruffat et al., “EBV latent membrane protein 1 is a negative regulator of TLR9,” Journal of Immunology, vol. 185, no. 11, pp. 6439–6447, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. G. Trinchieri, “Biology of natural killer cells,” Advances in Immunology, vol. 47, pp. 187–376, 1989. View at Google Scholar · View at Scopus
  81. M. A. Degli-Esposti and M. J. Smyth, “Close encounters of different kinds: dendritic cells and NK cells take centre stage,” Nature Reviews Immunology, vol. 5, no. 2, pp. 112–124, 2005. View at Publisher · View at Google Scholar · View at Scopus
  82. M. A. Cooper, T. A. Fehniger, and M. A. Caligiuri, “The biology of human natural killer-cell subsets,” Trends in Immunology, vol. 22, no. 11, pp. 633–640, 2001. View at Publisher · View at Google Scholar · View at Scopus
  83. T. A. Fehniger, M. A. Cooper, G. J. Nuovo et al., “CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity,” Blood, vol. 101, no. 8, pp. 3052–3057, 2003. View at Publisher · View at Google Scholar · View at Scopus
  84. D. Iwakiri, L. Zhou, M. Samanta et al., “Epstein-Barr virus (EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from toll-like receptor 3,” Journal of Experimental Medicine, vol. 206, no. 10, pp. 2091–2099, 2009. View at Publisher · View at Google Scholar · View at Scopus
  85. G. Ferlazzo, M. Pack, D. Thomas et al., “Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 47, pp. 16606–16611, 2004. View at Publisher · View at Google Scholar · View at Scopus
  86. T. Strowig, F. Brilot, F. Arrey et al., “Tonsilar NK cells restrict B cell transformation by the epstein-barr virus via IFN-γ,” PLoS Pathogens, vol. 4, no. 2, p. e27, 2008. View at Publisher · View at Google Scholar · View at Scopus
  87. L. Benoit, X. Wang, H. F. Pabst, J. Dutz, and R. Tan, “Defective NK cell activation in X-linked lymphoproliferative disease,” Journal of Immunology, vol. 165, no. 7, pp. 3549–3553, 2000. View at Google Scholar · View at Scopus
  88. O. Devergne, A. Coulomb-L'Herminé, F. Capel, M. Moussa, and F. Capron, “Expression of Epstein-Barr virus-induced gene 3, an interleukin-12 p40-related molecule, throughout human pregnancy: involvement of syncytiotrophoblasts and extravillous trophoblasts,” The American Journal of Pathology, vol. 159, no. 5, pp. 1763–1776, 2001. View at Google Scholar · View at Scopus
  89. F. Larousserie, E. Bardel, S. Pflanz et al., “Analysis of interleukin-27 (EBI3/p28) expression in Epstein-Barr virus- and human T-cell leukemia virus type 1-associated lymphomas: heterogeneous expression of EBI3 subunit by tumoral cells,” The American Journal of Pathology, vol. 166, no. 4, pp. 1217–1228, 2005. View at Google Scholar · View at Scopus
  90. F. Locatelli, D. Pende, R. Maccario, M. C. Mingari, A. Moretta, and L. Moretta, “Haploidentical hemopoietic stem cell transplantation for the treatment of high-risk leukemias: how NK cells make the difference,” Clinical Immunology, vol. 133, no. 2, pp. 171–178, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. P. Comoli, S. Basso, M. Zecca et al., “Preemptive therapy of EBV-related lymphoproliferative disease after pediatric haploidentical stem cell transplantation,” The American Journal of Transplantation, vol. 7, no. 6, pp. 1648–1655, 2007. View at Publisher · View at Google Scholar · View at Scopus
  92. M. A. Cassatella, S. Gasperini, and M. P. Russo, “Cytokine expression and release by neutrophils,” Annals of the New York Academy of Sciences, vol. 832, pp. 233–242, 1997. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Calattini, I. Sereti, P. Scheinberg, H. Kimura, R. W. Childs, and J. I. Cohen, “Detection of EBV genomes in plasmablasts/plasma cells and non-B cells in the blood of most patients with EBV lymphoproliferative disorders by using Immuno-FISH,” Blood, vol. 116, no. 22, pp. 4546–4559, 2010. View at Publisher · View at Google Scholar · View at Scopus
  94. H. Vallhov, C. Gutzeit, S. M. Johansson et al., “Exosomes containing glycoprotein 350 released by EBV-transformed B cells selectively target B cells through CD21 and block EBV infection in vitro,” Journal of Immunology, vol. 186, no. 1, pp. 73–82, 2011. View at Publisher · View at Google Scholar
  95. D. M. Pegtel, K. Cosmopoulos, D. A. Thorley-Lawson et al., “Functional delivery of viral miRNAs via exosomes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 14, pp. 6328–6333, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. K. F. Eriksson, L. Holmberg, and C. G. Bergstrand, “Infectious mononucleosis and agranulocytosis,” Scandinavian Journal of Infectious Diseases, vol. 11, no. 4, pp. 307–309, 1979. View at Google Scholar · View at Scopus
  97. W. P. Hammond, J. M. Harlan, and S. E. Steinberg, “Severe neutropenia in infectious mononucleosis,” Western Journal of Medicine, vol. 131, no. 2, pp. 92–97, 1979. View at Google Scholar · View at Scopus
  98. Y. Kagoya, A. Hangaishi, T. Takahashi, Y. Imai, and M. Kurokawa, “High-dose dexamethasone therapy for severe thrombocytopenia and neutropenia induced by EBV infectious mononucleosis,” International Journal of Hematology, vol. 91, no. 2, pp. 326–327, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. B. Larochelle, L. Flamand, P. Gourde, D. Beauchamp, and J. Gosselin, “Epstein-Barr virus infects and induces apoptosis in human neutrophils,” Blood, vol. 92, no. 1, pp. 291–299, 1998. View at Google Scholar · View at Scopus
  100. A. D. Beaulieu, R. Paquin, and J. Gosselin, “Epstein-Barr virus modulates de novo protein synthesis in human neutrophils,” Blood, vol. 86, no. 7, pp. 2789–2798, 1995. View at Google Scholar · View at Scopus
  101. W. P. Arena, M. Malyak, C. J. Guthridge, and C. Gabay, “Interleukin-1 receptor antagonist: role in biology,” Annual Review of Immunology, vol. 16, pp. 27–55, 1998. View at Publisher · View at Google Scholar
  102. C. J. Roberge, P. E. Poubelle, A. D. Beaulieu, D. Heitz, and J. Gosselin, “The IL-1 and IL-1 receptor antagonist (IL-1Ra) response of human neutrophils to EBV stimulation: preponderance of IL-1Ra detection,” Journal of Immunology, vol. 156, no. 12, pp. 4884–4891, 1996. View at Google Scholar · View at Scopus
  103. S. R. McColl, C. J. Roberge, B. Larochelle, and J. Gosselin, “EBV induces the production and release of IL-8 and macrophage inflammatory protein-1 alpha in human neutrophils,” Journal of Immunology, vol. 159, no. 12, pp. 6164–6168, 1997. View at Google Scholar
  104. M. Peters-Golden, C. Canetti, P. Mancuso, and M. J. Coffey, “Leukotrienes: underappreciated mediators of innate immune responses,” Journal of Immunology, vol. 174, no. 2, pp. 589–594, 2005. View at Google Scholar · View at Scopus
  105. J. Gosselin, P. Borgeat, and L. Flamand, “Leukotriene B4 protects latently infected mice against murine cytomegalovirus reactivation following allogeneic transplantation,” Journal of Immunology, vol. 174, no. 3, pp. 1587–1593, 2005. View at Google Scholar · View at Scopus
  106. D. R. Ratcliffe, S. L. Nolin, and E. B. Cramer, “Neutrophil interaction with influenza-infected epithelial cells,” Blood, vol. 72, no. 1, pp. 142–149, 1988. View at Google Scholar · View at Scopus
  107. E. Svedmyr, I. Ernberg, and J. Seeley, “Virologic, immunologic, and clinical observations on a patient during the incubation, acute, and convalescent phases of infectious mononucleosis,” Clinical Immunology and Immunopathology, vol. 30, no. 3, pp. 437–450, 1984. View at Google Scholar
  108. M. Savard, C. Bélanger, M. Tardif, P. Gourde, L. Flamand, and J. Gosselin, “Infection of primary human monocytes by Epstein-Barr virus,” Journal of Virology, vol. 74, no. 6, pp. 2612–2619, 2000. View at Publisher · View at Google Scholar
  109. M. Tardif, M. Savard, L. Flamand, and J. Gosselin, “Impaired protein kinase C activation/translocation in Epstein-Barr virus-infected monocytes,” Journal of Biological Chemistry, vol. 277, no. 27, pp. 24148–24154, 2002. View at Publisher · View at Google Scholar · View at Scopus
  110. Y.-L. Lin and M. Li, “Human cytomegalovirus and Epstein-Barr virus inhibit oral bacteria-induced macrophage activation and phagocytosis,” Oral Microbiology and Immunology, vol. 24, no. 3, pp. 243–248, 2009. View at Publisher · View at Google Scholar
  111. P. Speck, K. M. Haan, and R. Longnecker, “Epstein-Barr virus entry into cells,” Virology, vol. 277, no. 1, pp. 1–5, 2000. View at Publisher · View at Google Scholar · View at Scopus
  112. S. Tugizov, R. Herrera, P. Veluppillai, J. Greenspan, D. Greenspan, and J. M. Palefsky, “Epstein-Barr virus (EBV)-infected monocytes facilitate dissemination of EBV within the oral mucosal epithelium,” Journal of Virology, vol. 81, no. 11, pp. 5484–5496, 2007. View at Publisher · View at Google Scholar · View at Scopus
  113. L. Li, D. Liu, L. Hutt-Fletcher, A. Morgan, M. G. Masucci, and V. Levitsky, “Epstein-Barr virus inhibits the development of dendritic cells by promoting apoptosis of their monocyte precursors in the presence of granulocyte macrophage-colony-stimulating factor and interleukin-4,” Blood, vol. 99, no. 10, pp. 3725–3734, 2002. View at Publisher · View at Google Scholar · View at Scopus
  114. V. Wright-Browne, A. M. Schnee, M. A. Jenkins et al., “Serum cytokine levels in infectious mononucleosis at diagnosis and convalescencee,” Leukemia and Lymphoma, vol. 30, no. 5-6, pp. 583–589, 1998. View at Google Scholar · View at Scopus
  115. O. Janssen and D. Kabelitz, “Tumor necrosis factor selectively inhibits activation of human B cells by Epstein-Barr virus,” Journal of Immunology, vol. 140, no. 1, pp. 125–130, 1988. View at Google Scholar · View at Scopus
  116. C. J. Roberge, B. Larochelle, M. Rola-Pleszczynski, and J. Gosselin, “Epstein-Barr virus induces GM-CSF synthesis by monocytes: effect on EBV- induced IL-1 and IL-1 receptor antagonist production in neutrophils,” Virology, vol. 238, no. 2, pp. 344–352, 1997. View at Publisher · View at Google Scholar · View at Scopus
  117. J. Gosselin and P. Borgeat, “Epstein-Barr virus modulates 5-lipoxygenase product synthesis in human peripheral blood mononuclear cells,” Blood, vol. 89, no. 6, pp. 2122–2130, 1997. View at Google Scholar · View at Scopus
  118. J. Marcinkiewicz and B. M. Chain, “Differential cytokine regulation by eicosanoids in T cells primed by contact sensitisation with TNP,” Cellular Immunology, vol. 149, no. 2, pp. 303–314, 1993. View at Publisher · View at Google Scholar · View at Scopus
  119. E. R. Fedyk, D. M. Brown, and R. P. Phipps, “PGE2 regulation of B lymphocytes and T helper 1 and T helper 2 cells: induction of inflammatory versus allergic responses,” Advances in Experimental Medicine and Biology, vol. 407, pp. 237–242, 1996. View at Google Scholar · View at Scopus
  120. J. I. Cohen and K. Lekstrom, “Epstein-Barr virus BARF1 protein is dispensable for B-cell transformation and inhibits alpha interferon secretion from mononuclear cells,” Journal of Virology, vol. 73, no. 9, pp. 7627–7632, 1999. View at Google Scholar · View at Scopus
  121. P. Frangou, M. Buettner, and G. Niedobitek, “Epstein-Barr virus (EBV) infection in epithelial cells in vivo: rare detection of EBV replication in tongue mucosa but not in salivary glands,” Journal of Infectious Diseases, vol. 191, no. 2, pp. 238–242, 2005. View at Publisher · View at Google Scholar · View at Scopus
  122. V. Hadinoto, M. Shapiro, C. C. Sun, and D. A. Thorley-Lawson, “The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output,” PLoS Pathogens, vol. 5, no. 7, Article ID e1000496, 2009. View at Publisher · View at Google Scholar
  123. C. M. Tsang, G. Zhang, E. Seto et al., “Epstein-Barr virus infection in immortalized nasopharyngeal epithelial cells: regulation of infection and phenotypic characterization,” International Journal of Cancer, vol. 127, no. 7, pp. 1570–1583, 2010. View at Publisher · View at Google Scholar · View at Scopus
  124. L. S. Chesnokova, S. L. Nishimura, and L. M. Hutt-Fletcher, “Fusion of epithelial cells by Epstein-Barr virus proteins is triggered by binding of viral glycoproteins gHgL to integrins alphavbeta6 or alphavbeta8,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 48, pp. 20464–20469, 2009. View at Publisher · View at Google Scholar
  125. C. Shannon-Lowe and M. Rowe, “Epstein-Barr virus infection of polarized epithelial cells via the basolateral surface by memory B cell-mediated transfer infection,” PLoS Pathogens, vol. 7, no. 5, Article ID e1001338, 2011. View at Publisher · View at Google Scholar
  126. C. Keryer-Bibens, C. Pioche-Durieu, C. Villemant et al., “Exosomes released by EBV-infected nasopharyngeal carcinoma cells convey the viral Latent Membrane Protein 1 and the immunomodulatory protein galectin 9,” BMC Cancer, vol. 6, p. 283, 2006. View at Publisher · View at Google Scholar
  127. J. Flanagan, J. Middeldorp, and T. Sculley, “Localization of the Epstein-Barr virus protein LMP 1 to exosomes,” Journal of General Virology, vol. 84, no. 7, pp. 1871–1879, 2003. View at Publisher · View at Google Scholar · View at Scopus
  128. J. M. Middeldorp and D. M. Pegtel, “Multiple roles of LMP1 in Epstein-Barr virus induced immune escape,” Seminars in Cancer Biology, vol. 18, no. 6, pp. 388–396, 2008. View at Publisher · View at Google Scholar · View at Scopus
  129. K. M. Shah, S. E. Stewart, W. Wei et al., “The EBV-encoded latent membrane proteins, LMP2A and LMP2B, limit the actions of interferon by targeting interferon receptors for degradation,” Oncogene, vol. 28, no. 44, pp. 3903–3914, 2009. View at Publisher · View at Google Scholar · View at Scopus
  130. S. Bauer, T. Muller, and S. Hamm, “Pattern recognition by Toll-like receptors,” Advances in Experimental Medicine and Biology, vol. 653, pp. 15–34, 2009. View at Publisher · View at Google Scholar · View at Scopus
  131. S. Ning, “Innate immune modulation in EBV infection,” Herpesviridae, vol. 2, no. 1, p. 1, 2011. View at Google Scholar
  132. E. Gaudreault, S. Fiola, M. Olivier, and J. Gosselin, “Epstein-Barr virus induces MCP-1 secretion by human monocytes via TLR2,” Journal of Virology, vol. 81, no. 15, pp. 8016–8024, 2007. View at Publisher · View at Google Scholar · View at Scopus
  133. M. E. Ariza, R. Glaser, P. T. P. Kaumaya, C. Jones, and M. V. Williams, “The EBV-encoded dUTPase activates NF-κB through the TLR2 and MyD88-dependent signaling pathway,” Journal of Immunology, vol. 182, no. 2, pp. 851–859, 2009. View at Google Scholar · View at Scopus
  134. S. Fiola, D. Gosselin, K. Takada, and J. Gosselin, “TLR9 contributes to the recognition of EBV by primary monocytes and plasmacytoid dendritic cells,” Journal of Immunology, vol. 185, no. 6, pp. 3620–3631, 2010. View at Publisher · View at Google Scholar · View at Scopus
  135. H. L. Wai, S. Kireta, G. R. Russ, and P. T. H. Coates, “Human plasmacytoid dendritic cells regulate immune responses to Epstein-Barr virus (EBV) infection and delay EBV-related mortality in humanized NOD-SCID mice,” Blood, vol. 109, no. 3, pp. 1043–1050, 2007. View at Publisher · View at Google Scholar · View at Scopus
  136. U. A. Hasan, E. Bates, F. Takeshita et al., “TLR9 expression and function is abolished by the cervical cancer-associated human papillomavirus type 16,” Journal of Immunology, vol. 178, no. 5, pp. 3186–3197, 2007. View at Google Scholar · View at Scopus
  137. M. D. Rosa, E. Gottlieb, M. R. Lerner, and J. A. Steitz, “Striking similarities are exhibited by two small Epstein-Barr virus-encoded ribonucleic acids and the adenovirus-associated ribonucleic acids VAI and VAII,” Molecular and Cellular Biology, vol. 1, no. 9, pp. 785–796, 1981. View at Google Scholar · View at Scopus
  138. M. Samanta and K. Takada, “Modulation of innate immunity system by Epstein-Barr virus-encoded non-coding RNA and oncogenesis,” Cancer Science, vol. 101, no. 1, pp. 29–35, 2010. View at Publisher · View at Google Scholar · View at Scopus
  139. G. Gatto, A. Rossi, D. Rossi, S. Kroening, S. Bonatti, and M. Mallardo, “Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-κB pathway,” Nucleic Acids Research, vol. 36, no. 20, pp. 6608–6619, 2008. View at Publisher · View at Google Scholar · View at Scopus
  140. J. Hou, P. Wang, L. Lin et al., “MicroRNA-146a feedback inhibits RIG-I-dependent type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2,” Journal of Immunology, vol. 183, no. 3, pp. 2150–2158, 2009. View at Publisher · View at Google Scholar · View at Scopus
  141. F. J. Sheedy, E. Palsson-Mcdermott, E. J. Hennessy et al., “Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21,” Nature Immunology, vol. 11, no. 2, pp. 141–147, 2010. View at Publisher · View at Google Scholar · View at Scopus
  142. S. Iskra, M. Kalla, H. J. Delecluse, W. Hammerschmidt, and A. Moosmann, “Toll-like receptor agonists synergistically increase proliferation and activation of B cells by Epstein-Barr virus,” Journal of Virology, vol. 84, no. 7, pp. 3612–3623, 2010. View at Publisher · View at Google Scholar · View at Scopus
  143. H. H. Niller, H. Wolf, and J. Minarovits, “Regulation and dysregulation of Epstein-Barr virus latency: implications for the development of autoimmune diseases,” Autoimmunity, vol. 41, no. 4, pp. 298–328, 2008. View at Publisher · View at Google Scholar · View at Scopus
  144. A. D. Hislop, G. S. Taylor, D. Sauce, and A. B. Rickinson, “Cellular responses to viral infection in humans: lessons from Epstein-Barr virus,” Annual Review of Immunology, vol. 25, pp. 587–617, 2007. View at Publisher · View at Google Scholar · View at Scopus
  145. S. Pai and R. Khanna, “Role of LMP1 in immune control of EBV infection,” Seminars in Cancer Biology, vol. 11, no. 6, pp. 455–460, 2001. View at Publisher · View at Google Scholar · View at Scopus
  146. A. B. Rickinson and D. J. Moss, “Human cytotoxic T lymphocyte responses to Epstein-Barr virus infection,” Annual Review of Immunology, vol. 15, pp. 405–431, 1997. View at Publisher · View at Google Scholar · View at Scopus
  147. Y. Hoshino, T. Morishima, H. Kimura, K. Nishikawa, T. Tsurumi, and K. Kuzushima, “Antigen-driven expansion and contraction of CD8+-activated T cells in primary EBV infection,” Journal of Immunology, vol. 163, no. 10, pp. 5735–5740, 1999. View at Google Scholar · View at Scopus
  148. N. M. Steven, N. E. Annels, A. Kumar, A. M. Leese, M. G. Kurilla, and A. B. Rickinson, “Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus-induced cytotoxic T cell response,” Journal of Experimental Medicine, vol. 185, no. 9, pp. 1605–1617, 1997. View at Publisher · View at Google Scholar · View at Scopus
  149. M. F. Callan, L. Tan, N. Annels et al., “Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus in vivo,” Journal of Experimental Medicine, vol. 187, no. 9, pp. 1395–1402, 1998. View at Publisher · View at Google Scholar · View at Scopus
  150. S. Y. Gu, T. M. Huang, L. Ruan et al., “First EBV vaccine trial in humans using recombinant vaccinia virus expressing the major membrane antigen,” Developments in Biological Standardization, vol. 84, pp. 171–177, 1995. View at Google Scholar · View at Scopus
  151. R. Khanna, D. J. Moss, and S. R. Burrows, “Vaccine strategies against Epstein-Barr virus-associated diseases: lessons from studies on cytotoxic T-cell-mediated immune regulation,” Immunological Reviews, vol. 170, pp. 49–64, 1999. View at Publisher · View at Google Scholar · View at Scopus
  152. H. Hjalgrim, J. Askling, K. Rostgaard et al., “Characteristics of Hodgkin's lymphoma after infectious mononucleosis,” The New England Journal of Medicine, vol. 349, no. 14, pp. 1324–1332, 2003. View at Publisher · View at Google Scholar · View at Scopus
  153. H. E. Heslop, M. K. Brenner, C. Rooney et al., “Administration of neomycin resistance gene marked EBV specific cytotoxic T lymphocytes to recipients of mismatched-related or phenotypically similar unrelated donor marrow grafts,” Human Gene Therapy, vol. 5, no. 3, pp. 381–397, 1994. View at Google Scholar · View at Scopus
  154. C. M. Rooney, C. A. Smith, C. Y. C. Ng et al., “Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation,” The Lancet, vol. 345, no. 8941, pp. 9–13, 1995. View at Google Scholar · View at Scopus
  155. A. M. Leen and H. E. Heslop, “Cytotoxic T lymphocytes as immune-therapy in haematological practice,” The British Journal of Haematology, vol. 143, no. 2, pp. 169–179, 2008. View at Publisher · View at Google Scholar · View at Scopus
  156. C. L. Lin, W. F. Lo, T. H. Lee et al., “Immunization with Epstein-Barr Virus (EBV) peptide-pulsed dendritic cells induces functional CD8+ T-cell immunity and may lead to tumor regression in patients with EBV-positive nasopharyngeal carcinoma,” Cancer Research, vol. 62, no. 23, pp. 6952–6958, 2002. View at Google Scholar · View at Scopus
  157. C. M. Bollard, L. Aguilar, K. C. Straathof et al., “Cytotoxic T lymphocyte therapy for epstein-barr virus+ Hodgkin's disease,” Journal of Experimental Medicine, vol. 200, no. 12, pp. 1623–1633, 2004. View at Publisher · View at Google Scholar · View at Scopus
  158. J. Li, Q. Chen, H. Mo, Y. Zhang, Z. Huang, and Y. Zeng, “Immunophenotyping at the time of diagnosis distinguishes two groups of nasopharyngeal carcinoma patients: implications for adoptive immunotherapy,” International Journal of Biological Sciences, vol. 7, no. 5, pp. 607–617, 2011. View at Google Scholar
  159. C. Smith, L. Cooper, M. Burgess et al., “Functional reversion of antigen-specific CD8+ T cells from patients with Hodgkin lymphoma following in vitro stimulation with recombinant polyepitope,” Journal of Immunology, vol. 177, no. 7, pp. 4897–4906, 2006. View at Google Scholar · View at Scopus
  160. J. Duraiswamy, M. Bharadwaj, J. Tellam et al., “Induction of therapeutic T-cell responses to subdominant tumor-associated viral oncogene after immunization with replication-incompetent polyepitope adenovirus vaccine,” Cancer Research, vol. 64, no. 4, pp. 1483–1489, 2004. View at Publisher · View at Google Scholar · View at Scopus
  161. S. Landmeier, B. Altvater, S. Pscherer et al., “Activated human gammadelta T cells as stimulators of specific CD8+ T-cell responses to subdominant Epstein Barr virus epitopes: potential for immunotherapy of cancer,” Journal of Immunotherapy, vol. 32, no. 3, pp. 310–321, 2009. View at Google Scholar
  162. C. M. Bollard, S. Gottschalk, A. M. Leen et al., “Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer,” Blood, vol. 110, no. 8, pp. 2838–2845, 2007. View at Publisher · View at Google Scholar · View at Scopus
  163. C. U. Louis, K. Straathof, C. M. Bollard et al., “Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma,” Journal of Immunotherapy, vol. 33, no. 9, pp. 983–990, 2010. View at Publisher · View at Google Scholar · View at Scopus
  164. V. P. Lutzky, J. E. Davis, P. Crooks et al., “Optimization of LMP-specific CTL expansion for potential adoptive immunotherapy in NPC patients,” Immunology and Cell Biology, vol. 87, no. 6, pp. 481–488, 2009. View at Publisher · View at Google Scholar · View at Scopus
  165. C. U. Louis, K. Straath, C. M. Bollard et al., “Enhancing the in vivo expansion of adoptively transferred EBV- Specific CTL with lymphodepleting CD45 monoclonal antibodies in NPC patients,” Blood, vol. 113, no. 11, pp. 2442–2450, 2009. View at Publisher · View at Google Scholar · View at Scopus
  166. Y. Pan, J. Zhang, L. Zhou, J. Zuo, and Y. Zeng, “In vitro anti-tumor immune response induced by dendritic cells transfected with EBV-LMP2 recombinant adenovirus,” Biochemical and Biophysical Research Communications, vol. 347, no. 3, pp. 551–557, 2006. View at Publisher · View at Google Scholar
  167. S. P. Lee, A. T. C. Chan, S. T. Cheung et al., “CTL control of EBV in nasopharyngeal carcinoma (NPC): EBV-specific CTL responses in the blood and tumors of NPC patients and the antigen-processing function of the tumor cells,” Journal of Immunology, vol. 165, no. 1, pp. 573–582, 2000. View at Google Scholar · View at Scopus
  168. D. Martorelli, K. Houali, L. Caggiari et al., “Spontaneous T cell responses to Epstein-Barr virus-encoded BARF1 protein and derived peptides in patients with nasopharyngeal carcinoma: bases for improved immunotherapy,” International Journal of Cancer, vol. 123, no. 5, pp. 1100–1107, 2008. View at Publisher · View at Google Scholar · View at Scopus
  169. B. De Angelis, G. Dotti, C. Quintarelli et al., “Generation of Epstein-Barr virus-specific cytotoxic T lymphocytes resistant to the immunosuppressive drug tacrolimus (FK506),” Blood, vol. 114, no. 23, pp. 4784–4791, 2009. View at Publisher · View at Google Scholar · View at Scopus
  170. J. Brewin, C. Mancao, K. Straathof et al., “Generation of EBV-specific cytotoxic T cells that are resistant to calcineurin inhibitors for the treatment of posttransplantation lymphoproliferative disease,” Blood, vol. 114, no. 23, pp. 4792–4803, 2009. View at Publisher · View at Google Scholar · View at Scopus
  171. S. A. Rosenberg, M. T. Lotze, L. M. Muul et al., “Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer,” The New England Journal of Medicine, vol. 313, no. 23, pp. 1485–1492, 1985. View at Google Scholar
  172. S. A. Rosenberg, M. T. Lotze, L. M. Muul et al., “A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone,” The New England Journal of Medicine, vol. 316, no. 15, pp. 889–897, 1987. View at Google Scholar
  173. K. Margolin, “Cytokine therapy in cancer,” Expert Opinion on Biological Therapy, vol. 8, no. 10, pp. 1495–1505, 2008. View at Publisher · View at Google Scholar · View at Scopus
  174. J. S. Miller, J. Tessmer-Tuck, B. A. Pierson et al., “Low dose subcutaneous interleukin-2 after autologous transplantation generates sustained in vivo natural killer cell activity,” Biology of Blood and Marrow Transplantation, vol. 3, no. 1, pp. 34–44, 1997. View at Google Scholar · View at Scopus
  175. K. Kalwak, M. Ussowicz, E. Gorczynska et al., “Immunologic effects of intermediate-dose IL-2 i.v. after autologous hematopoietic cell transplantation in pediatric solid tumors,” Journal of Interferon and Cytokine Research, vol. 23, no. 4, pp. 173–181, 2003. View at Publisher · View at Google Scholar · View at Scopus
  176. D. J. Gottlieb, H. G. Prentice, A. B. Mehta et al., “Malignant plasma cells are sensitive to LAK cell lysis: pre-clinical and clinical studies of interleukin 2 in the treatment of multiple myeloma,” The British Journal of Haematology, vol. 75, no. 4, pp. 499–505, 1990. View at Google Scholar · View at Scopus
  177. C. Frohn, M. Hoppner, P. Schlenke, H. Kirchner, P. Koritke, and J. Luhm, “Anti-myeloma activity of natural killer lymphocytes,” The British Journal of Haematology, vol. 119, no. 3, pp. 660–664, 2002. View at Publisher · View at Google Scholar
  178. V. P. Khatri, R. A. Baiocchi, Z. P. Bernstein, and M. A. Caligiuri, “Immunotherapy with low-dose interleukin-2: rationale for prevention of immune-deficiency-associated cancer,” Cancer Journal from Scientific American, vol. 3, supplement 1, pp. S128–S136, 1997. View at Google Scholar
  179. Z. P. Bernstein, M. M. Porter, M. Gould et al., “Prolonged administration of low-dose interleukin-2 in human immunodeficiency virus-associated malignancy results in selective expansion of innate immune effectors without significant clinical toxicity,” Blood, vol. 86, no. 9, pp. 3287–3294, 1995. View at Google Scholar · View at Scopus
  180. T. A. Waldmann, “The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design,” Nature Reviews Immunology, vol. 6, no. 8, pp. 595–601, 2006. View at Publisher · View at Google Scholar · View at Scopus
  181. J. S. Miller, “Should natural killer cells be expanded in vivo or ex vivo to maximize their therapeutic potential?” Cytotherapy, vol. 11, no. 3, pp. 259–260, 2009. View at Publisher · View at Google Scholar · View at Scopus
  182. Y. Iwai, M. Ishida, Y. Tanaka, T. Okazaki, T. Honjo, and N. Minato, “Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 19, pp. 12293–12297, 2002. View at Publisher · View at Google Scholar · View at Scopus
  183. J. Liu, A. Hamrouni, D. Wolowiec et al., “Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-γ and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway,” Blood, vol. 110, no. 1, pp. 296–304, 2007. View at Publisher · View at Google Scholar · View at Scopus
  184. D. M. Benson Jr., C. E. Bakan, A. Mishra et al., “The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody,” Blood, vol. 116, no. 13, pp. 2286–2294, 2010. View at Publisher · View at Google Scholar · View at Scopus
  185. C. Petrovas, J. P. Casazza, J. M. Brenchley et al., “PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection,” Journal of Experimental Medicine, vol. 203, no. 10, pp. 2281–2292, 2006. View at Publisher · View at Google Scholar · View at Scopus
  186. T. C. Greenough, S. C. Campellone, R. Brody et al., “Programmed death-1 expression on epstein barr virus specific CD8+ T Cells varies by stage of infection, epitope specificity, and T-cell receptor usage,” PLoS One, vol. 5, no. 9, Article ID e12926, 2010. View at Publisher · View at Google Scholar · View at Scopus
  187. A. Merlo, R. Turrini, R. Dolcetti et al., “The interplay between Epstein-Barr virus and the immune system: a rationale for adoptive cell therapy of EBV-related disorders,” Haematologica, vol. 95, no. 10, pp. 1769–1777, 2010. View at Publisher · View at Google Scholar · View at Scopus
  188. S. M. Amos, H. J. Pegram, J. A. Westwood et al., “Adoptive immunotherapy combined with intratumoral TLR agonist delivery eradicates established melanoma in mice,” Cancer Immunology, Immunotherapy, vol. 60, no. 5, pp. 671–683, 2011. View at Publisher · View at Google Scholar
  189. L. Ruggeri, M. Capanni, E. Urbani et al., “Effectiveness of donor natural killer cell aloreactivity in mismatched hematopoietic transplants,” Science, vol. 295, no. 5562, pp. 2097–2100, 2002. View at Publisher · View at Google Scholar · View at Scopus
  190. H. G. Klingemann, “Natural killer cell-based immunotherapeutic strategies,” Cytotherapy, vol. 7, no. 1, pp. 16–22, 2005. View at Publisher · View at Google Scholar · View at Scopus
  191. H. G. Ljunggren and K. J. Malmberg, “Prospects for the use of NK cells in immunotherapy of human cancer,” Nature Reviews Immunology, vol. 7, no. 5, pp. 329–339, 2007. View at Publisher · View at Google Scholar · View at Scopus
  192. I. Y. Pappworth, E. C. Wang, and M. Rowe, “The switch from latent to productive infection in Epstein-Barr virus-infected B cells is associated with sensitization to NK cell killing,” Journal of Virology, vol. 81, no. 2, pp. 474–482, 2007. View at Publisher · View at Google Scholar · View at Scopus
  193. W. H. Feng, G. Hong, H. J. Delecluse, and S. C. Kenney, “Lytic induction therapy for Epstein-Barr virus-positive B-cell lymphomas,” Journal of Virology, vol. 78, no. 4, pp. 1893–1902, 2004. View at Publisher · View at Google Scholar · View at Scopus
  194. K. F. Hui and A. K. S. Chiang, “Suberoylanilide hydroxamic acid induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death,” International Journal of Cancer, vol. 126, no. 10, pp. 2479–2489, 2010. View at Publisher · View at Google Scholar · View at Scopus
  195. C. M. Shirley, J. Chen, M. Shamay et al., “Bortezomib induction of C/EBPbeta mediates Epstein-Barr virus lytic activation in Burkitt lymphoma,” Blood, vol. 117, no. 23, pp. 6297–6303, 2011. View at Google Scholar
  196. S. P. Perrine, O. Hermine, T. Small et al., “A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies,” Blood, vol. 109, no. 6, pp. 2571–2578, 2007. View at Publisher · View at Google Scholar · View at Scopus
  197. D. Baltimore, M. P. Boldin, R. M. O'Connell, D. S. Rao, and K. D. Taganov, “MicroRNAs: new regulators of immune cell development and function,” Nature Immunology, vol. 9, no. 8, pp. 839–845, 2008. View at Publisher · View at Google Scholar · View at Scopus
  198. H. Okada, G. Kohanbash, and M. T. Lotze, “MicroRNAs in immune regulation—opportunities for cancer immunotherapy,” International Journal of Biochemistry and Cell Biology, vol. 42, no. 8, pp. 1256–1261, 2010. View at Publisher · View at Google Scholar · View at Scopus
  199. A. Banerjee, F. Schambach, C. S. Dejong, S. M. Hammond, and S. L. Reiner, “Micro-RNA-155 inhibits IFN-γ signaling in CD4+ T cells,” European Journal of Immunology, vol. 40, no. 1, pp. 225–231, 2010. View at Publisher · View at Google Scholar · View at Scopus
  200. Q. J. Li, J. Chau, P. J. R. Ebert et al., “miR-181a is an intrinsic modulator of T cell sensitivity and selection,” Cell, vol. 129, no. 1, pp. 147–161, 2007. View at Publisher · View at Google Scholar · View at Scopus
  201. T. A. Fehniger, T. Wylie, E. Germino et al., “Next-generation sequencing identifies the natural killer cell microRNA transcriptome,” Genome Research, vol. 20, no. 11, pp. 1590–1604, 2010. View at Publisher · View at Google Scholar · View at Scopus
  202. N. A. Bezman, E. Cedars, D. F. Steiner, R. Blelloch, D. G. T. Hesslein, and L. L. Lanier, “Distinct requirements of microRNAs in NK cell activation, survival, and function,” Journal of Immunology, vol. 185, no. 7, pp. 3835–3846, 2010. View at Publisher · View at Google Scholar · View at Scopus
  203. A. L. Ellis-Connell, T. Iempridee, I. Xu, and J. E. Mertz, “Cellular microRNAs 200b and 429 regulate the Epstein-Barr virus switch between latency and lytic replication,” Journal of Virology, vol. 84, no. 19, pp. 10329–10343, 2010. View at Publisher · View at Google Scholar · View at Scopus