Regulation of immune responses to HPVinfection and during HPV-directed immunotherapy

Immunological Reviews

Volumn 239, Issue 1, 2011, Pages 85-98

  Bhat, Purnima ^a   Mattarollo, Stephen R ^a   Gosmann, Christina ^a   Frazer, Ian H ^a   Leggatt, Graham R ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

Cervical cancer; Immunoregulation; Immunosuppression; NKT cells; Papillomavirus infection

Indexed keywords

CYCLOOXYGENASE 2; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; TRANSFORMING GROWTH FACTOR BETA; VIRUS PROTEIN; WART VIRUS VACCINE;

ADAPTIVE IMMUNITY; ARTICLE; CANCER INCIDENCE; CARCINOGENESIS; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; HUMAN; IMMUNE RESPONSE; IMMUNOTHERAPY; INNATE IMMUNITY; MORTALITY; NATURAL KILLER T CELL; NONHUMAN; PAPILLOMAVIRUS INFECTION; PATHOGENESIS; PRIORITY JOURNAL; UTERINE CERVIX CANCER; WART VIRUS;

ADAPTIVE IMMUNITY; CYTOKINES; FEMALE; HUMAN PAPILLOMAVIRUS 16; HUMAN PAPILLOMAVIRUS 18; HUMANS; IMMUNITY, INNATE; IMMUNOTHERAPY; PAPILLOMAVIRIDAE; PAPILLOMAVIRUS INFECTIONS; PAPILLOMAVIRUS VACCINES; RISK FACTORS; UTERINE CERVICAL NEOPLASMS;

EID: 78650550224     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/j.1600-065X.2010.00966.x     Document Type: Article

References (147)

1. Frazer IH. Prevention of cervical cancer through papillomavirus vaccination. Nat Rev Immunol 2004;4:46-54.
2. Insinga RP, Dasbach EJ, Elbasha EH. Epidemiologic natural history and clinical management of Human Papillomavirus (HPV) Disease: a critical and systematic review of the literature in the development of an HPV dynamic transmission model. BMC Infect Dis 2009;9:119.
3. Koutsky L. Epidemiology of genital human papillomavirus infection. Am J Med 1997;102:3-8.
4. Curado MP, et al. eds (2007). Cancer Incidence in Five Continents, Vol. IX Lyon: IARC Scientific Publications 2010; 160.
5. National Cancer Institute UNIoH. Surveillance Epidemiology and End Results (SEER 17) 2005-2007. Available from.
6. Koshiol JE, et al. Time to clearance of human papillomavirus infection by type and human immunodeficiency virus serostatus. Int J Cancer 2006;119:1623-1629.
7. Syrjanen K, et al. Oral contraceptives are not an independent risk factor for cervical intraepithelial neoplasia or high-risk human papillomavirus infections. Anticancer Res 2006;26:4729-4740.
8. Collins S, Rollason TP, Young LS, Woodman CB. Cigarette smoking is an independent risk factor for cervical intraepithelial neoplasia in young women: a longitudinal study. Eur J Cancer 2010;46:405-411.
9. Bosch FX, de Sanjose S. The epidemiology of human papillomavirus infection and cervical cancer. Dis Markers 2007;23:213-227.
10. Moreno V, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet 2002;359:1085-1092.
11. Riley RR, Duensing S, Brake T, Munger K, Lambert PF, Arbeit JM. Dissection of human papillomavirus E6 and E7 function in transgenic mouse models of cervical carcinogenesis. Cancer Res 2003;63:4862-4871.
12. Zelmanowicz Ade M, et al. Family history as a co-factor for adenocarcinoma and squamous cell carcinoma of the uterine cervix: results from two studies conducted in Costa Rica and the United States. Int J Cancer 2005;116:599-605.
13. Magnusson PK, Sparen P, Gyllensten UB. Genetic link to cervical tumours. Nature 1999;400:29-30.
14. Leggatt GR, Frazer IH. HPV vaccines: the beginning of the end for cervical cancer. Curr Opin Immunol 2007;19:232-238.
15. Schiller JT, Day PM, Kines RC. Current understanding of the mechanism of HPV infection. Gynecol Oncol 2010;118:S12-17.
16. Romanczuk H, Howley PM. Disruption of either the E1 or the E2 regulatory gene of human papillomavirus type 16 increases viral immortalization capacity. Proc Natl Acad Sci USA 1992;89:3159-3163.
17. Klingelhutz AJ, Foster SA, McDougall JK. Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature 1996;380:79-82.
18. Liu X, Dakic A, Zhang Y, Dai Y, Chen R, Schlegel R. HPV E6 protein interacts physically and functionally with the cellular telomerase complex. Proc Natl Acad Sci USA 2009;106:18780-18785.
19. Carter JJ, et al. Comparison of human papillomavirus types 16, 18, and 6 capsid antibody responses following incident infection. J Infect Dis 2000;181:1911-1919.
20. Carter JJ, et al. Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites. Cancer Res 2001;61:1934-1940.
21. Wang SS, et al. Determinants of human papillomavirus 16 serological conversion and persistence in a population-based cohort of 10 000 women in Costa Rica. Br J Cancer 2004;91:1269-1274.
22. Insinga RP, et al. Incidence, duration, and reappearance of type-specific cervical human papillomavirus infections in young women. Cancer Epidemiol Biomarkers Prev 2010;19:1585-1594.
23. Jenison SA, Yu XP, Valentine JM, Galloway DA. Characterization of human antibody-reactive epitopes encoded by human papillomavirus types 16 and 18. J Virol 1991;65:1208-1218.
24. Mandelson MT, et al. The association of human papillomavirus antibodies with cervical cancer risk. Cancer Epidemiol Biomarkers Prev 1992;1:281-286.
25. Zhou J, Sun XY, Stenzel DJ, Frazer IH. Expression of vaccinia recombinant HPV 16 L1 and L2 ORF proteins in epithelial cells is sufficient for assembly of HPV virion-like particles. Virology 1991;185:251-257.
26. Kirnbauer R, et al. Efficient self-assembly of human papillomavirus type 16 L1 and L1-L2 into virus-like particles. J Virol 1993;67:6929-6936.
27. Khan K, et al. Preventing cervical cancer overviews of the National Breast and Cervical Cancer Early Detection Program and 2 US immunization programs. Cancer 2008;113:3004-3012.
28. Coleman N, et al. Immunological events in regressing genital warts. Am J Clin Pathol 1994;102:768-774.
29. de Vos van Steenwijk PJ, et al. An unexpectedly large polyclonal repertoire of HPV-specific T cells is poised for action in patients with cervical cancer. Cancer Res 2010;70:2707-2717.
30. Molling JW, et al. CD4(+)CD25hi regulatory T-cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasia. Int J Cancer 2007;121:1749-1755.
31. Ovestad IT, et al. Local immune response in the microenvironment of CIN2-3 with and without spontaneous regression. Mod Pathol 2010;23:1231-1240.
32. Jaafar F, et al. Correlation of CXCL12 expression and FoxP3+ cell infiltration with human papillomavirus infection and clinicopathological progression of cervical cancer. Am J Pathol 2009;175:1525-1535.
33. Monnier-Benoit S, et al. Immunohistochemical analysis of CD4+ and CD8+ T-cell subsets in high risk human papillomavirus-associated pre-malignant and malignant lesions of the uterine cervix. Gynecol Oncol 2006;102:22-31.
34. Woo YL, et al. A prospective study on the natural course of low-grade squamous intraepithelial lesions and the presence of HPV16 E2-, E6- and E7-specific T-cell responses. Int J Cancer 2010;126:133-141.
35. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell 2010;140:805-820.
36. Franchi L, Eigenbrod T, Munoz-Planillo R, Nunez G. The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol 2009;10:241-247.
37. Schroder K, Tschopp J. The inflammasomes. Cell 2010;140:821-832.
38. Schroder K, Zhou R, Tschopp J. The NLRP3 inflammasome: a sensor for metabolic danger? Science 2010;327:296-300.
39. Tschopp J, Schroder K. NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat Rev Immunol 2010;10:210-215.
40. Arend WP, Palmer G, Gabay C. IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev 2008;223:20-38.
41. Davidson B, Goldberg I, Kopolovic J. Inflammatory response in cervical intraepithelial neoplasia and squamous cell carcinoma of the uterine cervix. Pathol Res Pract 1997;193:491-495.
42. Rock KL, Latz E, Ontiveros F, Kono H. The sterile inflammatory response. Annu Rev Immunol 2010;28:321-342.
43. Brennan K, Bowie AG. Activation of host pattern recognition receptors by viruses. Curr Opin Microbiol 2010;13:503-507.
44. Lee JW, et al. Increased toll-like receptor 9 expression in cervical neoplasia. Mol Carcinog 2007;46:941-947.
45. Daud II, Scott ME, Ma Y, Shiboski S, Farhat S, Moscicki AB. Association between toll-like receptors expression and human papillomavirus type 16 persistence. Int J Cancer 2010; doi: 10.1002/ijc.25400.
46. Khunamornpong S, et al. Cyclooxygenase-2 expression in squamous cell carcinoma of the uterine cervix is associated with lymph node metastasis. Gynecol Oncol 2009;112:241-247.
47. Beglin M, Melar-New M, Laimins L. Human papillomaviruses and the interferon response. J Interferon Cytokine Res 2009;29:629-635.
48. Textor S, et al. NF-kappa B-dependent upregulation of ICAM-1 by HPV16-E6/E7 facilitates NK cell/target cell interaction. Int J Cancer 2010; doi: 10.1002/ijc.25442.
49. Hasan UA, et al. TLR9 expression and function is abolished by the cervical cancer-associated human papillomavirus type 16. J Immunol 2007;178:3186-3197.
50. Yu L, Wang L, Li M, Zhong J, Wang Z, Chen S. Expression of toll-like receptor 4 is down-regulated during progression of cervical neoplasia. Cancer Immunol Immunother 2010;59:1021-1028.
51. Hadis U, Leggatt GR, Thomas R, Frazer IH, Kovacs EM. IL-1 signalling determines the fate of skin grafts expressing non-self protein in keratinocytes. Exp Dermatol 2010;19:723-729.
52. Mattarollo SR, Rahimpour A, Choyce A, Godfrey DI, Leggatt GR, Frazer IH. Invariant NKT cells in hyperplastic skin induce a local immune suppressive environment by IFN-gamma production. J Immunol 2010;184:1242-1250.
53. Watanabe H, et al. Activation of the IL-1beta-processing inflammasome is involved in contact hypersensitivity. J Invest Dermatol 2007;127:1956-1963.
54. Feldmeyer L, Keller M, Niklaus G, Hohl D, Werner S, Beer HD. The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes. Curr Biol 2007;17:1140-1145.
55. Nestle FO, Di Meglio P, Qin JZ, Nickoloff BJ. Skin immune sentinels in health and disease. Nat Rev Immunol 2009;9:679-691.
56. Naik SM, et al. Human keratinocytes constitutively express interleukin-18 and secrete biologically active interleukin-18 after treatment with pro-inflammatory mediators and dinitrochlorobenzene. J Invest Dermatol 1999;113:766-772.
57. Stoll S, et al. Production of IL-18 (IFN-gamma-inducing factor) messenger RNA and functional protein by murine keratinocytes. J Immunol 1997;159:298-302.
58. Johnston JB, et al. A poxvirus-encoded pyrin domain protein interacts with ASC-1 to inhibit host inflammatory and apoptotic responses to infection. Immunity 2005;23:587-598.
59. Cilloniz C, et al. Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes. PLoS Pathog 2009;5:e1000604.
60. Cho YS, et al. Down modulation of IL-18 expression by human papillomavirus type 16 E6 oncogene via binding to IL-18. FEBS Lett 2001;501:139-145.
61. Lee SJ, et al. Both E6 and E7 oncoproteins of human papillomavirus 16 inhibit IL-18-induced IFN-gamma production in human peripheral blood mononuclear and NK cells. J Immunol 2001;167:497-504.
62. Kobayashi A, Weinberg V, Darragh T, Smith-McCune K. Evolving immunosuppressive microenvironment during human cervical carcinogenesis. Mucosal Immunol 2008;1:412-420.
63. Mota F, Rayment N, Chong S, Singer A, Chain B. The antigen-presenting environment in normal and human papillomavirus (HPV)-related premalignant cervical epithelium. Clin Exp Immunol 1999;116:33-40.
64. Bermudez-Morales VH, Gutierrez LX, Alcocer-Gonzalez JM, Burguete A, Madrid-Marina V. Correlation between IL-10 gene expression and HPV infection in cervical cancer: a mechanism for immune response escape. Cancer Invest 2008;26:1037-1043.
65. Bhairavabhotla RK, Verm V, Tongaonkar H, Shastri S, Dinshaw K, Chiplunkar S. Role of IL-10 in immune suppression in cervical cancer. Indian J Biochem Biophys 2007;44:350-356.
66. Alcocer-Gonzalez JM, et al. In vivo expression of immunosuppressive cytokines in human papillomavirus-transformed cervical cancer cells. Viral Immunol 2006;19:481-491.
67. Kobayashi A, et al. Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection. Cancer Res 2004;64:6766-6774.
68. Castle PE, et al. Cervical concentrations of interleukin-10 and interleukin-12 do not correlate with plasma levels. J Clin Immunol 2002;22:23-27.
69. El-Sherif AM, Seth R, Tighe PJ, Jenkins D. Quantitative analysis of IL-10 and IFN-gamma mRNA levels in normal cervix and human papillomavirus type 16 associated cervical precancer. J Pathol 2001;195:179-185.
70. Zoodsma M, et al. Interleukin-10 and Fas polymorphisms and susceptibility for (pre)neoplastic cervical disease. Int J Gynecol Cancer 2005;15(Suppl. 3):282-290.
71. Arany I, Grattendick KG, Tyring SK. Interleukin-10 induces transcription of the early promoter of human papillomavirus type 16 (HPV16) through the 5'-segment of the upstream regulatory region (URR). Antiviral Res 2002;55:331-339.
72. Liu XS, Leerberg J, MacDonald K, Leggatt GR, Frazer IH. IFN-gamma promotes generation of IL-10 secreting CD4+ T cells that suppress generation of CD8 responses in an antigen-experienced host. J Immunol 2009;183:51-58.
73. Liu XS, et al. IL-10 mediates suppression of the CD8 T cell IFN-gamma response to a novel viral epitope in a primed host. J Immunol 2003;171:4765-4772.
74. Peralta-Zaragoza O, Bermudez-Morales V, Gutierrez-Xicotencatl L, Alcocer-Gonzalez J, Recillas-Targa F, Madrid-Marina V. E6 and E7 oncoproteins from human papillomavirus type 16 induce activation of human transforming growth factor beta1 promoter throughout Sp1 recognition sequence. Viral Immunol 2006;19:468-480.
75. Xu Q, et al. Effects of human papillomavirus type 16 E7 protein on the growth of cervical carcinoma cells and immuno-escape through the TGF-beta1 signaling pathway. Gynecol Oncol 2006;101:132-139.
76. Donalisio M, Cornaglia M, Landolfo S, Lembo D. TGF-beta1 and IL-4 downregulate human papillomavirus-16 oncogene expression but have differential effects on the malignant phenotype of cervical carcinoma cells. Virus Res 2008;132:253-256.
77. Habig M, Smola H, Dole VS, Derynck R, Pfister H, Smola-Hess S. E7 proteins from high- and low-risk human papillomaviruses bind to TGF-beta-regulated Smad proteins and inhibit their transcriptional activity. Arch Virol 2006;151:1961-1972.
78. Lee DK, Kim BC, Kim IY, Cho EA, Satterwhite DJ, Kim SJ. The human papilloma virus E7 oncoprotein inhibits transforming growth factor-beta signaling by blocking binding of the Smad complex to its target sequence. J Biol Chem 2002;277:38557-38564.
79. Diaz-Chavez J, Hernandez-Pando R, Lambert PF, Gariglio P. Down-regulation of transforming growth factor-beta type II receptor (TGF-betaRII) protein and mRNA expression in cervical cancer. Mol Cancer 2008;7:3.
80. Kim S, et al. Systemic blockade of transforming growth factor-beta signaling augments the efficacy of immunogene therapy. Cancer Res 2008;68:10247-10256.
81. Dunn LA, et al. Presentation of the HPV16E7 protein by skin grafts is insufficient to allow graft rejection in an E7-primed animal. Virology 1997;235:94-103.
82. Havard L, Delvenne P, Frare P, Boniver J, Giannini SL. Differential production of cytokines and activation of NF-kappaB in HPV-transformed keratinocytes. Virology 2002;298:271-285.
83. Tamandani DM, Sobti RC, Shekari M, Kaur S, Huria A. Impact of polymorphism in IL-1RA gene on the risk of cervical cancer. Arch Gynecol Obstet 2008;277:527-533.
84. Gangwar R, Mittal B, Mittal RD. Association of interleukin-6 -174G>C promoter polymorphism with risk of cervical cancer. Int J Biol Markers 2009;24:11-16.
85. Singh H, Sachan R, Jain M, Mittal B. CCR5-Delta32 polymorphism and susceptibility to cervical cancer: association with early stage of cervical cancer. Oncol Res 2008;17:87-91.
86. Brown CE, et al. Tumor-derived chemokine MCP-1/CCL2 is sufficient for mediating tumor tropism of adoptively transferred T cells. J Immunol 2007;179:3332-3341.
87. Scott ME, Ma Y, Kuzmich L, Moscicki AB. Diminished IFN-gamma and IL-10 and elevated Foxp3 mRNA expression in the cervix are associated with CIN 2 or 3. Int J Cancer 2009;124:1379-1383.
88. Jordanova ES, et al. Human leukocyte antigen class I, MHC class I chain-related molecule A, and CD8+/regulatory T-cell ratio: which variable determines survival of cervical cancer patients? Clin Cancer Res 2008;14:2028-2035.
89. Fattorossi A, et al. Lymphocyte composition of tumor draining lymph nodes from cervical and endometrial cancer patients. Gynecol Oncol 2004;92:106-115.
90. Narayan S, et al. Epithelial expression of human papillomavirus type 16 E7 protein results in peripheral CD8 T-cell suppression mediated by CD4+CD25+ T cells. Eur J Immunol 2009;39:481-490.
91. Tuve S, et al. Combination of tumor site-located CTL-associated antigen-4 blockade and systemic regulatory T-cell depletion induces tumor-destructive immune responses. Cancer Res 2007;67:5929-5939.
92. Bellone M, et al. iNKT cells control mouse spontaneous carcinoma independently of tumor-specific cytotoxic T cells. PLoS ONE 2010;5:e8646.
93. Crowe NY, Smyth MJ, Godfrey DI. A critical role for natural killer T cells in immunosurveillance of methylcholanthrene-induced sarcomas. J Exp Med 2002;196:119-127.
94. Park JM, Terabe M, Donaldson DD, Forni G, Berzofsky JA. Natural immunosurveillance against spontaneous, autochthonous breast cancers revealed and enhanced by blockade of IL-13-mediated negative regulation. Cancer Immunol Immunother 2008;57:907-912.
95. Smyth MJ, et al. Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med 2000;191:661-668.
96. Swann JB, et al. Type I NKT cells suppress tumors in mice caused by p53 loss. Blood 2009;113:6382-6385.
97. Terabe M, et al. CD1d-restricted natural killer T cells can down-regulate tumor immunosurveillance independent of interleukin-4 receptor-signal transducer and activator of transcription 6 or transforming growth factor-beta. Cancer Res 2006;66:3869-3875.
98. Terabe M, et al. NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol 2000;1:515-520.
99. Terabe M, et al. A nonclassical non-Vα14Jα18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance. J Exp Med 2005;202:1627-1633.
100. Crowe NY, et al. Differential antitumor immunity mediated by NKT cell subsets in vivo. J Exp Med 2005;202:1279-1288.
101. Godfrey DI, Stankovic S, Baxter AG. Raising the NKT cell family. Nat Immunol 2010;11:197-206.
102. Ambrosino E, et al. Cross-regulation between type I and type II NKT cells in regulating tumor immunity: a new immunoregulatory axis. J Immunol 2007;179:5126-5136.
103. Moodycliffe AM, Nghiem D, Clydesdale G, Ullrich SE. Immune suppression and skin cancer development: regulation by NKT cells. Nat Immunol 2000;1:521-525.
104. Falcone M, et al. Up-regulation of CD1d expression restores the immunoregulatory function of NKT cells and prevents autoimmune diabetes in nonobese diabetic mice. J Immunol 2004;172:5908-5916.
105. Mars LT, et al. Cutting edge: V alpha 14-J alpha 281 NKT cells naturally regulate experimental autoimmune encephalomyelitis in nonobese diabetic mice. J Immunol 2002;168:6007-6011.
106. Sonoda KH, Taniguchi M, Stein-Streilein J. Long-term survival of corneal allografts is dependent on intact CD1d-reactive NKT cells. J Immunol 2002;168:2028-2034.
107. Seino KI, et al. Requirement for natural killer T (NKT) cells in the induction of allograft tolerance. Proc Natl Acad Sci USA 2001;98:2577-2581.
108. Jiang X, Kojo S, Harada M, Ohkohchi N, Taniguchi M, Seino KI. Mechanism of NKT cell-mediated transplant tolerance. Am J Transplant 2007;7:1482-1490.
109. Li W, et al. Cooperation of invariant NKT cells and CD4+CD25+ T regulatory cells in prevention of autoimmune diabetes in non-obese diabetic mice treated with alpha-galactosylceramide. Acta Biochim Biophys Sin (Shanghai) 2008;40:381-390.
110. Nakamura T, et al. CD4+ NKT cells, but not conventional CD4+ T cells, are required to generate efferent CD8+ T regulatory cells following antigen inoculation in an immune-privileged site. J Immunol 2003;171:1266-1271.
111. Onzuka T, et al. Role of the cytokine profiles produced by invariant natural killer T cells in the initial phase of cyclophosphamide-induced tolerance. Transplantation 2008;86:1301-1310.
112. Sonoda KH, Faunce DE, Taniguchi M, Exley M, Balk S, Stein-Streilein J. NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance. J Immunol 2001;166:42-50.
113. Watte CM, Nakamura T, Lau CH, Ortaldo JR, Stein-Streilein J. Ly49 C/I-dependent NKT cell-derived IL-10 is required for corneal graft survival and peripheral tolerance. J Leukoc Biol 2008;83:928-935.
114. Pastor S, Minguela A, Mi W, Ward ES. Autoantigen immunization at different sites reveals a role for anti-inflammatory effects of IFN-gamma in regulating susceptibility to experimental autoimmune encephalomyelitis. J Immunol 2009;182:5268-5275.
115. Willenborg DO, Fordham SA, Staykova MA, Ramshaw IA, Cowden WB. IFN-gamma is critical to the control of murine autoimmune encephalomyelitis and regulates both in the periphery and in the target tissue: a possible role for nitric oxide. J Immunol 1999;163:5278-5286.
116. Minguela A, Pastor S, Mi W, Richardson JA, Ward ES. Feedback regulation of murine autoimmunity via dominant anti-inflammatory effects of interferon gamma. J Immunol 2007;178:134-144.
117. Kawana K, et al. Expression of CD1d and ligand-induced cytokine production are tissue-specific in mucosal epithelia of the human lower reproductive tract. Infect Immun 2008;76:3011-3018.
118. Bonish B, et al. Overexpression of CD1d by keratinocytes in psoriasis and CD1d-dependent IFN-gamma production by NK-T cells. J Immunol 2000;165:4076-4085.
119. Colgan SP, Morales VM, Madara JL, Polischuk JE, Balk SP, Blumberg RS. IFN-gamma modulates CD1d surface expression on intestinal epithelia. Am J Physiol 1996;271:C276-283.
120. Koelle DM, Corey L. Herpes simplex: insights on pathogenesis and possible vaccines. Annu Rev Med 2008;59:381-395.
121. Ashrafi GH, Haghshenas M, Marchetti B, Campo MS. E5 protein of human papillomavirus 16 downregulates HLA class I and interacts with the heavy chain via its first hydrophobic domain. Int J Cancer 2006;119:2105-2112.
122. Leggatt GR, Dunn LA, De Kluyver RL, Stewart T, Frazer IH. Interferon-gamma enhances cytotoxic T lymphocyte recognition of endogenous peptide in keratinocytes without lowering the requirement for surface peptide. Immunol Cell Biol 2002;80:415-424.
123. Zhou F, Frazer IH, Leggatt GR. Keratinocytes efficiently process endogenous antigens for cytotoxic T-cell mediated lysis. Exp Dermatol 2009;18:1053-1059.
124. Park JS, Kim EJ, Kwon HJ, Hwang ES, Namkoong SE, Um SJ. Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis. J Biol Chem 2000;275:6764-6769.
125. Um SJ, Rhyu JW, Kim EJ, Jeon KC, Hwang ES, Park JS. Abrogation of IRF-1 response by high-risk HPV E7 protein in vivo. Cancer Lett 2002;179:205-212.
126. Antonsson A, Payne E, Hengst K, McMillan NA. The human papillomavirus type 16 E7 protein binds human interferon regulatory factor-9 via a novel PEST domain required for transformation. J Interferon Cytokine Res 2006;26:455-461.
127. Barnard P, Payne E, McMillan NA. The human papillomavirus E7 protein is able to inhibit the antiviral and anti-growth functions of interferon-alpha. Virology 2000;277:411-419.
128. Cordano P, et al. The E6E7 oncoproteins of cutaneous human papillomavirus type 38 interfere with the interferon pathway. Virology 2008;377:408-418.
129. Bottley G, Watherston OG, Hiew YL, Norrild B, Cook GP, Blair GE. High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells. Oncogene 2008;27:1794-1799.
130. Li W, et al. Down-regulation of HLA class I antigen in human papillomavirus type 16 E7 expressing HaCaT cells: correlate with TAP-1 expression. Int J Gynecol Cancer 2010;20:227-232.
131. Smahel M, Sima P, Ludvikova V, Marinov I, Pokorna D, Vonka V. Immunisation with modified HPV16 E7 genes against mouse oncogenic TC-1 cell sublines with downregulated expression of MHC class I molecules. Vaccine 2003;21:1125-1136.
132. Vambutas A, DeVoti J, Pinn W, Steinberg BM, Bonagura VR. Interaction of human papillomavirus type 11 E7 protein with TAP-1 results in the reduction of ATP-dependent peptide transport. Clin Immunol 2001;101:94-99.
133. Vambutas A, et al. Polymorphism of transporter associated with antigen presentation 1 as a potential determinant for severity of disease in recurrent respiratory papillomatosis caused by human papillomavirus types 6 and 11. J Infect Dis 2004;189:871-879.
134. Ritz U, Momburg F, Pilch H, Huber C, Maeurer MJ, Seliger B. Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma. Int J Oncol 2001;19:1211-1220.
135. Evans M, et al. Antigen processing defects in cervical carcinomas limit the presentation of a CTL epitope from human papillomavirus 16 E6. J Immunol 2001;167:5420-5428.
136. Georgopoulos NT, Proffitt JL, Blair GE. Transcriptional regulation of the major histocompatibility complex (MHC) class I heavy chain, TAP1 and LMP2 genes by the human papillomavirus (HPV) type 6b, 16 and 18 E7 oncoproteins. Oncogene 2000;19:4930-4935.
137. Zehbe I, Hohn H, Pilch H, Neukirch C, Freitag K, Maeurer MJ. Differential MHC class II component expression in HPV-positive cervical cancer cells: implication for immune surveillance. Int J Cancer 2005;117:807-815.
138. Giannini SL, Hubert P, Doyen J, Boniver J, Delvenne P. Influence of the mucosal epithelium microenvironment on Langerhans cells: implications for the development of squamous intraepithelial lesions of the cervix. Int J Cancer 2002;97:654-659.
139. Wei L, Gravitt PE, Song H, Maldonado AM, Ozbun MA. Nitric oxide induces early viral transcription coincident with increased DNA damage and mutation rates in human papillomavirus-infected cells. Cancer Res 2009;69:4878-4884.
140. Sappayatosok K, et al. Expression of pro-inflammatory protein, iNOS, VEGF and COX-2 in oral squamous cell carcinoma (OSCC), relationship with angiogenesis and their clinico-pathological correlation. Med Oral Patol Oral Cir Bucal 2009;14:E319-324.
141. Mazibrada J, et al. Interaction between inflammation and angiogenesis during different stages of cervical carcinogenesis. Gynecol Oncol 2008;108:112-120.
142. Young JL, Jazaeri AA, Darus CJ, Modesitt SC. Cyclooxygenase-2 in cervical neoplasia: a review. Gynecol Oncol 2008;109:140-145.
143. Woodworth CD, McMullin E, Iglesias M, Plowman GD. Interleukin 1 alpha and tumor necrosis factor alpha stimulate autocrine amphiregulin expression and proliferation of human papillomavirus-immortalized and carcinoma-derived cervical epithelial cells. Proc Natl Acad Sci USA 1995;92:2840-2844.
144. Fahey LM, Raff AB, Da Silva DM, Kast WM. Reversal of human papillomavirus-specific T cell immune suppression through TLR agonist treatment of Langerhans cells exposed to human papillomavirus type 16. J Immunol 2009;182:2919-2928.
145. Zhong J, Hadis U, De Kluyver R, Leggatt GR, Fernando GJ, Frazer IH. TLR7 stimulation augments T effector-mediated rejection of skin expressing neo-self antigen in keratinocytes. Eur J Immunol 2008;38:73-81.
146. Garland SM. Imiquimod Curr Opin Infect Dis 2003;16:85-89.
147. Terlou A, et al. Imiquimod induced clearance of HPV is associated with normalization of immune cell counts in usual type vulvar intraepithelial neoplasia. Int J Cancer 2010;doi:.