Table of Contents Author Guidelines Submit a Manuscript
Scientifica
Volume 2014 (2014), Article ID 125450, 20 pages
http://dx.doi.org/10.1155/2014/125450
Review Article

Immune Response in Thyroid Cancer: Widening the Boundaries

Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences, University of Campinas (FCM-Unicamp), Rua Tessália Vieira de Camargo 126, Barão Geraldo, 13083-970 Campinas, SP, Brazil

Received 3 March 2014; Accepted 19 June 2014; Published 25 September 2014

Academic Editor: Daiqing Liao

Copyright © 2014 Laura Sterian Ward. 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. S. Matsubayashi, K. Kawai, Y. Matsumoto et al., “The correlation between papillary thyroid carcinoma and lymphocytic infiltration in the thyroid gland,” Journal of Clinical Endocrinology and Metabolism, vol. 80, no. 12, pp. 3421–3424, 1995. View at Google Scholar · View at Scopus
  2. J. Modi, A. Patel, R. Terrell, R. M. Tuttle, and G. L. Francis, “Papillary thyroid carcinomas from young adults and children contain a mixture of lymphocytes,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 9, pp. 4418–4425, 2003. View at Publisher · View at Google Scholar · View at Scopus
  3. Y. Yano, H. Shibuya, W. Kitagawa, M. Nagahama, K. Sugino, and K. Ito, “Recent outcome of grave's disease patients with papillary thyroid cancer,” European Journal of Endocrinology, vol. 157, no. 3, pp. 325–329, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. J. Hagström, A. Heikkilä, P. Siironen et al., “TLR-4 expression and decrease in chronic inflammation: indicators of aggressive follicular thyroid carcinoma,” Journal of Clinical Pathology, vol. 65, no. 4, pp. 333–338, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. J. D. French, Z. J. Weber, D. L. Fretwell, S. Said, J. P. Klopper, and B. R. Haugen, “Tumor-associated lymphocytes and increased FoxP3+ regulatory T cell frequency correlate with more aggressive papillary thyroid cancer,” Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 5, pp. 2325–2333, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. S. Gupta, A. Patel, A. Folstad et al., “Infiltration of differentiated thyroid carcinoma by proliferating lymphocytes is associated with improved disease-free survival for children and young adults,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 3, pp. 1346–1354, 2001. View at Publisher · View at Google Scholar · View at Scopus
  7. L. L. Cunha and L. S. Ward, “Concurrent lymphocytic thyroiditis is associated to less aggressive papillary thyroid carcinomas,” European Archives of Oto-Rhino-Laryngology, vol. 269, no. 2, pp. 699–700, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. J. A. Sipos and E. L. Mazzaferri, “Thyroid cancer epidemiology and prognostic variables,” Clinical Oncology, vol. 22, no. 6, pp. 395–404, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. R. Siegel, D. Naishadham, and A. Jemal, “Cancer statistics, 2013,” CA: A Cancer Journal for Clinicians, vol. 63, no. 1, pp. 11–30, 2013. View at Publisher · View at Google Scholar · View at Scopus
  10. G. Pellegriti, F. Frasca, C. Regalbuto, S. Squatrito, and R. Vigneri, “Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors,” Journal of Cancer Epidemiology, vol. 2013, Article ID 965212, 10 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  11. M. C. Mahoney, S. Lawvere, K. L. Falkner et al., “Thyroid cancer incidence trends in Belarus: examining the impact of Chernobyl,” International Journal of Epidemiology, vol. 33, no. 5, pp. 1025–1033, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. D. Williams, “Radiation carcinogenesis: lessons from Chernobyl,” Oncogene, vol. 27, no. 2, pp. S9–S18, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. S. J. Schonfeld, C. Lee, and A. B. de González, “Medical exposure to radiation and thyroid cancer,” Clinical Oncology, vol. 23, no. 4, pp. 244–250, 2011. View at Publisher · View at Google Scholar · View at Scopus
  14. A. K. Ng, L. B. Kenney, E. S. Gilbert, and L. B. Travis, “Secondary malignancies across the age spectrum,” Seminars in Radiation Oncology, vol. 20, no. 1, pp. 67–78, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. K. Hamatani, H. Eguchi, R. Ito et al., “RET/PTC rearrangements preferentially occurred in papillary thyroid cancer among atomic bomb survivors exposed to high radiation dose,” Cancer Research, vol. 68, no. 17, pp. 7176–7182, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. Y. E. Nikiforov, “Is ionizing radiation responsible for the increasing incidence of thyroid cancer?” Cancer, vol. 116, no. 7, pp. 1626–1628, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. Y. E. Nikiforov, J. M. Rowland, K. E. Bove, H. Monforte-Munoz, and J. A. Fagin, “Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children,” Cancer Research, vol. 57, no. 9, pp. 1690–1694, 1997. View at Google Scholar · View at Scopus
  18. L. Wartofsky, “Increasing world incidence of thyroid cancer: increased detection or higher radiation exposure?” Hormones, vol. 9, no. 2, pp. 103–108, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. B. Dijkstra, R. S. Prichard, A. Lee et al., “Changing patterns of thyroid carcinoma,” Irish Journal of Medical Science, vol. 176, no. 2, pp. 87–90, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. E. Cardis, A. Kesminiene, V. Ivanov et al., “Risk of thyroid cancer after exposure to 131I in childhood,” Journal of the National Cancer Institute, vol. 97, no. 10, pp. 724–732, 2005. View at Publisher · View at Google Scholar · View at Scopus
  21. Y. Ito and A. Miyauchi, “Prognostic factors and therapeutic strategies for differentiated carcinomas of the thyroid,” Endocrine Journal, vol. 56, no. 2, pp. 177–192, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. A. Pinchera, “Thyroid incidentalomas,” Hormone Research, vol. 68, supplement 5, pp. 199–201, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. T. Rago, E. Fiore, M. Scutari et al., “Male sex, single nodularity, and young age are associated with the risk of finding a papillary thyroid cancer on fine-needle aspiration cytology in a large series of patients with nodular thyroid disease,” European Journal of Endocrinology, vol. 162, no. 4, pp. 763–770, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. R. L. Witt and A. M. McNamara, “Prognostic factors in mortality and morbidity in patients with differentiated thyroid cancer,” Ear, Nose and Throat Journal, vol. 81, no. 12, pp. 856–863, 2002. View at Google Scholar · View at Scopus
  25. K.-C. Loh, F. S. Greenspan, L. Gee, T. R. Miller, and P. P. B. Yeo, “Pathological tumor-node-metastasis (pTNM) staging for papillary and follicular thyroid carcinomas: a retrospective analysis of 700 patients,” The Journal of Clinical Endocrinology & Metabolism, vol. 82, no. 11, pp. 3553–3562, 1997. View at Publisher · View at Google Scholar · View at Scopus
  26. S. L. Oyer, V. A. Smith, and E. J. Lentsch, “Sex is not an independent risk factor for survival in differentiated thyroid cancer,” Laryngoscope, vol. 123, no. 11, pp. 2913–2919, 2013. View at Publisher · View at Google Scholar · View at Scopus
  27. G. Riesco-Eizaguirre and P. Santisteban, “Molecular biology of thyroid cancer initiation,” Clinical and Translational Oncology, vol. 9, no. 11, pp. 686–693, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. R. Ciampi, J. A. Knauf, R. Kerler et al., “Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer,” Journal of Clinical Investigation, vol. 115, no. 1, pp. 94–101, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. C. Carta, S. Moretti, L. Passeri et al., “Genotyping of an Italian papillary thyroid carcinoma cohort revealed high prevalence of BRAF mutations, absence of RAS mutations and allowed the detection of a new mutation of BRAF oncoprotein (BRAFV599Ins),” Clinical Endocrinology, vol. 64, no. 1, pp. 105–109, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. P. Hou, D. Liu, and M. M. Xing, “Functional characterization of the T1799-1801del and A1799-1816ins BRAF mutations in papillary thyroid cancer,” Cell Cycle, vol. 6, no. 3, pp. 377–379, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. R. P. Tufano, G. V. Teixeira, J. Bishop, K. A. Carson, and M. Xing, “BRAF mutation in papillary thyroid cancer and its value in tailoring initial treatment: a systematic review and meta-analysis,” Medicine, vol. 91, no. 5, pp. 274–286, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. M. Romitti, L. Ceolin, D. R. Siqueira, C. V. Ferreira, S. M. Wajner, and A. L. Maia, “Signaling pathways in follicular cell-derived thyroid carcinomas (Review),” International Journal of Oncology, vol. 42, no. 1, pp. 19–28, 2013. View at Publisher · View at Google Scholar · View at Scopus
  33. L. Fugazzola, S. Pilotti, A. Pinchera et al., “Oncogenic rearrangements of the RET proto-oncogene in papillary thyroid carcinomas from children exposed to the Chernobyl nuclear accident,” Cancer Research, vol. 55, no. 23, pp. 5617–5620, 1995. View at Google Scholar · View at Scopus
  34. A. Bounacer, R. Wicker, B. Caillou et al., “High prevalence of activating ret proto-oncogene rearrangements, in thyroid tumors from patients who had received external radiation,” Oncogene, vol. 15, no. 11, pp. 1263–1273, 1997. View at Publisher · View at Google Scholar · View at Scopus
  35. I. Bongarzone, L. Fugazzola, P. Vigneri et al., “Age-related activation of the tyrosine kinase receptor protooncogenes RET and NTRK1 in papillary thyroid carcinoma,” Journal of Clinical Endocrinology and Metabolism, vol. 81, no. 5, pp. 2006–2009, 1996. View at Publisher · View at Google Scholar · View at Scopus
  36. F. Carlomagno, D. Vitagliano, T. Guida et al., “ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases,” Cancer Research, vol. 62, no. 24, pp. 7284–7290, 2002. View at Google Scholar · View at Scopus
  37. F. Carlomagno, D. Vitagliano, T. Guida et al., “Efficient inhibition of RET/papillary thyroid carcinoma oncogenic kinases by 4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2),” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 4, pp. 1897–1902, 2003. View at Publisher · View at Google Scholar · View at Scopus
  38. C. Lanzi, G. Cassinelli, G. Cuccuru et al., “Inactivation of Ret/Ptc1 oncoprotein and inhibition of papillary thyroid carcinoma cell proliferation by indolinone RPI-1,” Cellular and Molecular Life Sciences, vol. 60, no. 7, pp. 1449–1459, 2003. View at Publisher · View at Google Scholar · View at Scopus
  39. H. Namba, S. A. Rubin, and J. A. Fagin, “Point mutations of ras oncogenes are an early event in thyroid tumorigenesis,” Molecular Endocrinology, vol. 4, no. 10, pp. 1474–1479, 1990. View at Publisher · View at Google Scholar · View at Scopus
  40. N. R. Lemoine, E. S. Mayall, F. S. Wyllie et al., “Activated ras oncogenes in human thyroid cancers,” Cancer Research, vol. 48, no. 16, pp. 4459–4463, 1988. View at Google Scholar · View at Scopus
  41. P. Hou, D. X. Liu, Y. Shan et al., “Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer,” Clinical Cancer Research, vol. 13, no. 4, pp. 1161–1170, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. G. García-Rostán, A. M. Costa, I. Pereira-Castro et al., “Mutation of the PIK3CA gene in anaplastic thyroid cancer,” Cancer Research, vol. 65, no. 22, pp. 10199–10207, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. Y. Wang, P. Hou, H. Yu et al., “High prevalence and mutual exclusivity of genetic alterations in the phosphatidylinositol-3-kinase/akt pathway in thyroid tumors,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 6, pp. 2387–2390, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. T. Kondo, S. Ezzat, and S. L. Asa, “Pathogenetic mechanisms in thyroid follicular-cell neoplasia,” Nature Reviews Cancer, vol. 6, no. 4, pp. 292–306, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. Y. E. Nikiforov, “Genetic alterations involved in the transition from well-differentiated to poorly differentiated and anaplastic thyroid carcinomas,” Endocrine Pathology, vol. 15, no. 4, pp. 319–327, 2004. View at Publisher · View at Google Scholar · View at Scopus
  46. T. Ito, T. Seyama, T. Mizuno et al., “Unique association of p53 mutations with undifferentiated but not with differentiated carcinomas of the thyroid gland,” Cancer Research, vol. 52, no. 5, pp. 1369–1371, 1992. View at Google Scholar · View at Scopus
  47. S. Battista, M. L. Martelli, M. Fedele et al., “A mutated p53 gene alters thyroid cell differentiation,” Oncogene, vol. 11, no. 10, pp. 2029–2037, 1995. View at Google Scholar · View at Scopus
  48. J. M. Kirkwood, L. H. Butterfield, A. A. Tarhini, H. Zarour, P. Kalinski, and S. Ferrone, “Immunotherapy of cancer in 2012,” CA Cancer Journal for Clinicians, vol. 62, no. 5, pp. 309–335, 2012. View at Publisher · View at Google Scholar · View at Scopus
  49. R. Kim, M. Emi, and K. Tanabe, “Cancer immunoediting from immune surveillance to immune escape,” Immunology, vol. 121, no. 1, pp. 1–14, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. J. B. A. G. Haanen, A. Baars, R. Gomez et al., “Melanoma-specific tumor-infiltrating lymphocytes but not circulating melanoma-specific T cells may predict survival in resected advanced-stage melanoma patients,” Cancer Immunology, Immunotherapy, vol. 55, no. 4, pp. 451–458, 2006. View at Publisher · View at Google Scholar · View at Scopus
  51. E. Sato, S. H. Olson, J. Ahn et al., “Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 51, pp. 18538–18543, 2005. View at Publisher · View at Google Scholar
  52. M. Yoshimoto, G. Sakamoto, and Y. Ohashi, “Time dependency of the influence of prognostic factors on relapse in breast cancer,” Cancer, vol. 72, no. 10, pp. 2993–3001, 1993. View at Google Scholar
  53. T. E. Reichert, R. Day, E. M. Wagner, and T. L. Whiteside, “Absent or low expression of the ζ chain in T cells at the tumor site correlates with poor survival in patients with oral carcinoma,” Cancer Research, vol. 58, no. 23, pp. 5344–5347, 1998. View at Google Scholar · View at Scopus
  54. M. Yasunaga, Y. Tabira, K. Nakano et al., “Accelerated growth signals and low tumor-infiltrating lymphocyte levels predict poor outcome in T4 esophageal squamous cell carcinoma,” Annals of Thoracic Surgery, vol. 70, no. 5, pp. 1634–1640, 2000. View at Publisher · View at Google Scholar · View at Scopus
  55. Y. Naito, K. Saito, K. Shiiba et al., “CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer,” Cancer Research, vol. 58, no. 16, pp. 3491–3494, 1998. View at Google Scholar · View at Scopus
  56. F. M. Burnet, “Immunological surveillance in neoplasia,” Transplantation Reviews, vol. 7, pp. 3–25, 1971. View at Google Scholar · View at Scopus
  57. L. Thomas, “On immunosurveillance in human cancer,” Yale Journal of Biology and Medicine, vol. 55, no. 3-4, pp. 329–333, 1982. View at Google Scholar · View at Scopus
  58. G. Klein, “Immune surveillance—a powerful mechanism with a limited range,” National Cancer Institute Monograph, vol. 44, pp. 109–113, 1976. View at Google Scholar · View at Scopus
  59. J. D. Lewis, B. D. Reilly, and R. K. Bright, “Tumor-associated antigens: from discovery to immunity,” International Reviews of Immunology, vol. 22, no. 2, pp. 81–112, 2003. View at Publisher · View at Google Scholar · View at Scopus
  60. A. M. Neville, A. M. Mackay, J. Westwood, C. Turberville, and D. J. Laurence, “Human tumour-associated and tumour-specific antigens: some concepts in relation to clinical oncology,” Journal of Clinical Pathology, vol. 6, pp. 102–112, 1975. View at Google Scholar · View at Scopus
  61. G. P. Dunn, A. T. Bruce, H. Ikeda, L. J. Old, and R. D. Schreiber, “Cancer immunoediting: from immunosurveillance to tumor escape,” Nature Immunology, vol. 3, no. 11, pp. 991–998, 2002. View at Publisher · View at Google Scholar · View at Scopus
  62. J. D. French, “Revisiting immune-based therapies for aggressive follicular cell-derived thyroid cancers,” Thyroid, vol. 23, no. 5, pp. 529–542, 2013. View at Publisher · View at Google Scholar · View at Scopus
  63. I. Poschke, D. Mougiakakos, and R. Kiessling, “Camouflage and sabotage: tumor escape from the immune system,” Cancer Immunology, Immunotherapy, vol. 60, no. 8, pp. 1161–1171, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. G. Zhou, C. G. Drake, and H. I. Levitsky, “Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines,” Blood, vol. 107, no. 2, pp. 628–636, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. B. Bogen, “Peripheral T cell tolerance as a tumor escape mechanism: Deletion of CD4+ T cells specific for a monoclonal immunoglobulin idiotype secreted by a plasmacytoma,” European Journal of Immunology, vol. 26, no. 11, pp. 2671–2679, 1996. View at Publisher · View at Google Scholar · View at Scopus
  66. K. Staveley-O'Carroll, E. Sotomayor, J. Montgomery et al., “Induction of antigen-specific T cell anergy: an early event in the course of tumor progression,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 3, pp. 1178–1183, 1998. View at Publisher · View at Google Scholar · View at Scopus
  67. G. Willimsky and T. Blankenstein, “Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance,” Nature, vol. 437, no. 7055, pp. 141–146, 2005. View at Publisher · View at Google Scholar · View at Scopus
  68. P. P. Lee, C. Yee, P. A. Savage et al., “Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients,” Nature Medicine, vol. 5, no. 6, pp. 677–685, 1999. View at Publisher · View at Google Scholar · View at Scopus
  69. R. Mortarini, A. Piris, A. Maurichi et al., “Lack of terminally differentiated tumor-specific CD8+ T cells at tumor site in spite of antitumor immunity to self-antigens in human metastatic melanoma,” Cancer Research, vol. 63, no. 10, pp. 2535–2545, 2003. View at Google Scholar · View at Scopus
  70. C. L. Burek and N. R. Rose, “Autoimmune thyroiditis and ROS,” Autoimmunity Reviews, vol. 7, no. 7, pp. 530–537, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. J. C. Flynn, D. J. McCormick, V. Brusic et al., “Pathogenic human thyroglobulin peptides in HLA-DR3 transgenic mouse model of autoimmune thyroiditis,” Cellular Immunology, vol. 229, no. 2, pp. 79–85, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. A. Konturek, M. Barczyński, W. Wierzchowski, M. Stopa, and W. Nowak, “Coexistence of papillary thyroid cancer with Hashimoto thyroiditis,” Langenbeck's Archives of Surgery, vol. 398, no. 3, pp. 389–394, 2013. View at Publisher · View at Google Scholar · View at Scopus
  73. Y. Tomer and F. Menconi, “Interferon induced thyroiditis,” Best Practice & Research: Clinical Endocrinology & Metabolism, vol. 23, no. 6, pp. 703–712, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. F. Pacifico and A. Leonardi, “Role of NF-κB in thyroid cancer,” Molecular and Cellular Endocrinology, vol. 321, no. 1, pp. 29–35, 2010. View at Publisher · View at Google Scholar · View at Scopus
  75. F. Balkwill and A. Mantovani, “Inflammation and cancer: back to Virchow?” The Lancet, vol. 357, no. 9255, pp. 539–545, 2001. View at Publisher · View at Google Scholar · View at Scopus
  76. P. Correa, “Human gastric carcinogenesis: a multistep and multifactorial process—first American Cancer Society Award lecture on cancer epidemiology and prevention,” Cancer Research, vol. 52, no. 24, pp. 6735–6740, 1992. View at Google Scholar · View at Scopus
  77. A. Ekbom, C. Helmick, M. Zack, and H.-O. Adami, “Ulcerative colitis and colorectal cancer: a population-based study,” The New England Journal of Medicine, vol. 323, no. 18, pp. 1228–1233, 1990. View at Publisher · View at Google Scholar · View at Scopus
  78. A. C. de Vries, J. Haringsma, and E. J. Kuipers, “The detection, surveillance and treatment of premalignant gastric lesions related to Helicobacter pyloriinfection,” Helicobacter, vol. 12, no. 1, pp. 1–15, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. A. C. de Vries, N. C. T. van Grieken, C. W. N. Looman et al., “Gastric cancer risk in patients with premalignant gastric lesions: a nationwide cohort study in the Netherlands,” Gastroenterology, vol. 134, no. 4, pp. 945–952, 2008. View at Publisher · View at Google Scholar · View at Scopus
  80. M. E. Dailey, S. Lindsay, and R. Skahen, “Relation of thyroid neoplasms to Hashimoto disease of the thyroid gland,” A.M.A. Archives of Surgery, vol. 70, no. 2, pp. 291–297, 1955. View at Google Scholar
  81. M. H. Chui, C. A. Cassol, S. L. Asa, and O. Mete, “Follicular epithelial dysplasia of the thyroid: morphological and immunohistochemical characterization of a putative preneoplastic lesion to papillary thyroid carcinoma in chronic lymphocytic thyroiditis,” Virchows Archiv, vol. 462, no. 5, pp. 557–563, 2013. View at Publisher · View at Google Scholar · View at Scopus
  82. L. E. Holm, H. Blomgren, and T. Lowhagen, “Cancer risks in patients with chronic lymphocytic thyroiditis,” The New England Journal of Medicine, vol. 312, no. 10, pp. 601–604, 1985. View at Publisher · View at Google Scholar · View at Scopus
  83. E. Hyjek and P. G. Isaacson, “Primary B cell lymphoma of the thyroid and its relationship to Hashimoto's Thyroiditis,” Human Pathology, vol. 19, no. 11, pp. 1315–1326, 1988. View at Publisher · View at Google Scholar · View at Scopus
  84. N. Motoi and Y. Ozawa, “Malignant T-cell lymphoma of the thyroid gland associated with Hashimoto's thyroiditis,” Pathology International, vol. 55, no. 7, pp. 425–430, 2005. View at Publisher · View at Google Scholar · View at Scopus
  85. K. Itoh and N. Maruchi, “Breast cancer in patients with Hashimoto's thyroiditis,” The Lancet, vol. 2, no. 7945, pp. 1119–1121, 1975. View at Google Scholar · View at Scopus
  86. J. A. Bluestone and A. K. Abbas, “Natural versus adaptive regulatory T cells,” Nature Reviews Immunology, vol. 3, no. 3, pp. 253–257, 2003. View at Publisher · View at Google Scholar · View at Scopus
  87. A. S. Dighe, E. Richards, L. J. Old, and R. D. Schreiber, “Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFNγ receptors,” Immunity, vol. 1, no. 6, pp. 447–456, 1994. View at Publisher · View at Google Scholar · View at Scopus
  88. T.-T. Tan and L. M. Coussens, “Humoral immunity, inflammation and cancer,” Current Opinion in Immunology, vol. 19, no. 2, pp. 209–216, 2007. View at Publisher · View at Google Scholar · View at Scopus
  89. F. M. Burnet, “Virology as an independent science,” The Medical Journal of Australia, vol. 2, no. 22, pp. 841–845, 1953. View at Google Scholar · View at Scopus
  90. F. Boi, M. L. Lai, B. Marziani, L. Minerba, G. Faa, and S. Mariotti, “High prevalence of suspicious cytology in thyroid nodules associated with positive thyroid autoantibodies,” European Journal of Endocrinology, vol. 153, no. 5, pp. 637–642, 2005. View at Publisher · View at Google Scholar · View at Scopus
  91. M. Erdogan, N. Erdem, S. Cetinkalp et al., “Demographic, clinical, laboratory, ultrasonographic, and cytological features of patients with Hashimoto’s thyroiditis: results of a university hospital of 769 patients in Turkey,” Endocrine, vol. 36, no. 3, pp. 486–490, 2009. View at Publisher · View at Google Scholar · View at Scopus
  92. C. Anil, S. Goksel, and A. Gursoy, “Hashimoto's thyroiditis is not associated with increased risk of thyroid cancer in patients with thyroid nodules: a single-center prospective study,” Thyroid, vol. 20, no. 6, pp. 601–606, 2010. View at Publisher · View at Google Scholar · View at Scopus
  93. Y.-K. Chen, C.-L. Lin, F. T.-F. Cheng, F.-C. Sung, and C.-H. Kao, “Cancer risk in patients with Hashimoto's thyroiditis: a nationwide cohort study,” British Journal of Cancer, vol. 109, no. 9, pp. 2496–2501, 2013. View at Publisher · View at Google Scholar · View at Scopus
  94. G. Pellegriti, A. Belfiore, D. Giuffrida, L. Lupo, and R. Vigneri, “Outcome of differentiated thyroid cancer in Graves' patients,” Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 8, pp. 2805–2809, 1998. View at Publisher · View at Google Scholar · View at Scopus
  95. O. Ozaki, K. Ito, K. Kobayashi, K. Toshima, H. Iwasaki, and T. Yashiro, “Thyroid carcinoma in Graves' disease,” World Journal of Surgery, vol. 14, no. 3, pp. 437–440, 1990. View at Publisher · View at Google Scholar · View at Scopus
  96. K. Kashima, S. Yokoyama, S. Noguchi et al., “Chronic thyroiditis as a favorable prognostic factor in papillary thyroid carcinoma,” Thyroid, vol. 8, no. 3, pp. 197–202, 1998. View at Publisher · View at Google Scholar · View at Scopus
  97. K.-C. Loh, F. S. Greenspan, F. Dong, T. R. Miller, and P. P. B. Yeo, “Influence of lymphocytic thyroiditis on the prognostic outcome of patients with papillary thyroid carcinoma,” The Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 2, pp. 458–463, 1999. View at Publisher · View at Google Scholar · View at Scopus
  98. Y.-H. Yoon, H. J. Kim, J. W. Lee, J. M. Kim, and B. S. Koo, “The clinicopathologic differences in papillary thyroid carcinoma with or without co-existing chronic lymphocytic thyroiditis,” European Archives of Oto-Rhino-Laryngology, vol. 269, no. 3, pp. 1013–1017, 2012. View at Publisher · View at Google Scholar · View at Scopus
  99. L. L. Cunha and L. S. Ward, “Comments on ‘well-differentiated thyroid carcinoma with concomitant Hashimoto's thyroiditis present with less aggressive clinical stage and low recurrence’,” Endocrine Pathology, vol. 22, no. 3, pp. 172–173, 2011. View at Publisher · View at Google Scholar · View at Scopus
  100. B. Y. Huang, C. Hseuh, T. C. Chao, K. J. Lin, and J. D. Lin, “Well-differentiated thyroid carcinoma with concomitant Hashimoto's thyroiditis present with less aggressive clinical stage and low recurrence,” Endocrine Pathology, vol. 22, no. 3, pp. 144–149, 2011. View at Publisher · View at Google Scholar · View at Scopus
  101. S. Dvorkin, E. Robenshtok, D. Hirsch, Y. Strenov, I. Shimon, and C. A. Benbassat, “Differentiated thyroid cancer is associated with less aggressive disease and better outcome in patients with coexisting hashimotos thyroiditis,” Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 6, pp. 2409–2414, 2013. View at Publisher · View at Google Scholar · View at Scopus
  102. Y. Lun, X. Wu, Q. Xia et al., “Hashimoto's thyroiditis as a risk factor of papillary thyroid cancer may improve cancer prognosis,” Otolaryngology—Head and Neck Surgery, vol. 148, no. 3, pp. 396–402, 2013. View at Publisher · View at Google Scholar · View at Scopus
  103. N. Harii, C. J. Lewis, V. Vasko et al., “Thyrocytes express a functional Toll-like receptor 3: overexpression can be induced by viral infection and reversed by phenylmethimazole and is associated with Hashimoto's autoimmune thyroiditis,” Molecular Endocrinology, vol. 19, no. 5, pp. 1231–1250, 2005. View at Publisher · View at Google Scholar · View at Scopus
  104. K. Takeda and S. Akira, “Microbial recognition by Toll-like receptors,” Journal of Dermatological Science, vol. 34, no. 2, pp. 73–82, 2004. View at Publisher · View at Google Scholar · View at Scopus
  105. D. M. Underhill, “Toll-like receptors: networking for success,” European Journal of Immunology, vol. 33, no. 7, pp. 1767–1775, 2003. View at Publisher · View at Google Scholar · View at Scopus
  106. G. M. Barton and R. Medzhitov, “Toll-like receptor signaling pathways,” Science, vol. 300, no. 5625, pp. 1524–1525, 2003. View at Publisher · View at Google Scholar · View at Scopus
  107. K. Takeda, T. Kaisho, and S. Akira, “Toll-like receptors,” Annual Review of Immunology, vol. 21, pp. 335–376, 2003. View at Publisher · View at Google Scholar · View at Scopus
  108. M. Muzio, D. Bosisio, N. Polentarutti et al., “Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells,” The Journal of Immunology, vol. 164, no. 11, pp. 5998–6004, 2000. View at Publisher · View at Google Scholar · View at Scopus
  109. K. D. McCall, N. Harii, C. J. Lewis et al., “High basal levels of functional Toll-Like Receptor 3 (TLR3) and noncanonical Wnt5a are expressed in papillary thyroid cancer and are coordinately decreased by phenylmethimazole together with cell proliferation and migration,” Endocrinology, vol. 148, no. 9, pp. 4226–4237, 2007. View at Publisher · View at Google Scholar · View at Scopus
  110. A. Wirtschafter, R. Schmidt, D. Rosen et al., “Expression of the RET/PTC fusion gene as a marker for papillary carcinoma in Hashimoto’s thyroiditis,” Laryngoscope, vol. 107, no. 1, pp. 95–100, 1997. View at Publisher · View at Google Scholar · View at Scopus
  111. O. M. Sheils, J. J. O'Leary, V. Uhlmann, K. Lüttich, and E. C. Sweeney, “ret/PTC-1 activation in Hashimoto thyroiditis,” International Journal of Surgical Pathology, vol. 8, no. 3, pp. 185–189, 2000. View at Publisher · View at Google Scholar · View at Scopus
  112. R. Elisei, C. Romei, T. Vorontsova et al., “RET/PTC rearrangements in thyroid nodules: Studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 7, pp. 3211–3216, 2001. View at Publisher · View at Google Scholar · View at Scopus
  113. M. Muzza, D. Degl'Innocenti, C. Colombo et al., “The tight relationship between papillary thyroid cancer, autoimmunity and inflammation: clinical and molecular studies,” Clinical Endocrinology, vol. 72, no. 5, pp. 702–708, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. K. J. Rhoden, K. Unger, G. Salvatore et al., “RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes: follicular cells of Hashimoto's thyroiditis share low-level recombination events with a subset of papillary carcinoma,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 6, pp. 2414–2423, 2006. View at Publisher · View at Google Scholar · View at Scopus
  115. D.-Y. Kang, K.-H. Kim, J.-M. Kim et al., “High prevalence of RET, RAS, and ERK expression in Hashimoto's thyroiditis and in papillary thyroid carcinoma in the Korean population,” Thyroid, vol. 17, no. 11, pp. 1031–1038, 2007. View at Publisher · View at Google Scholar · View at Scopus
  116. V. Guarino, M. D. Castellone, E. Avilla, and R. M. Melillo, “Thyroid cancer and inflammation,” Molecular and Cellular Endocrinology, vol. 321, no. 1, pp. 94–102, 2010. View at Publisher · View at Google Scholar · View at Scopus
  117. L. M. Coussens and Z. Werb, “Inflammation and cancer,” Nature, vol. 420, no. 6917, pp. 860–867, 2002. View at Publisher · View at Google Scholar · View at Scopus
  118. F. Colotta, P. Allavena, A. Sica, C. Garlanda, and A. Mantovani, “Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability,” Carcinogenesis, vol. 30, no. 7, pp. 1073–1081, 2009. View at Publisher · View at Google Scholar · View at Scopus
  119. M. D. Castellone, A. M. Cirafici, G. de Vita et al., “Ras-mediated apoptosis of PC CL 3 rat thyroid cells induced by RET/PTC oncogenes,” Oncogene, vol. 22, no. 2, pp. 246–255, 2003. View at Publisher · View at Google Scholar · View at Scopus
  120. J. Wang, J. A. Knauf, S. Basu et al., “Conditional expression of RET/PTC induces a weak oncogenic drive in thyroid PCCL3 cells and inhibits thyrotropin action at multiple levels,” Molecular Endocrinology, vol. 17, no. 7, pp. 1425–1436, 2003. View at Publisher · View at Google Scholar · View at Scopus
  121. G. Stassi, M. Todaro, M. Zerilli et al., “Thyroid cancer resistance to chemotherapeutic drugs via autocrine production of interleukin-4 and interleukin-10,” Cancer Research, vol. 63, no. 20, pp. 6784–6790, 2003. View at Google Scholar · View at Scopus
  122. C. Conticello, F. Pedini, A. Zeuner et al., “IL-4 protects tumor cells from Anti-CD95 and chemotherapeutic agents via up-regulation of antiapoptotic proteins,” Journal of Immunology, vol. 172, no. 9, pp. 5467–5477, 2004. View at Publisher · View at Google Scholar · View at Scopus
  123. M. Todaro, Y. Lombardo, M. G. Francipane et al., “Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4,” Cell Death and Differentiation, vol. 15, no. 4, pp. 762–772, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. E. Puxeddu, J. A. Knauf, M. A. Sartor et al., “RET/PTC-induced gene expression in thyroid PCCL3 cells reveals early activation of genes involved in regulation of the immune response,” Endocrine-Related Cancer, vol. 12, no. 2, pp. 319–334, 2005. View at Publisher · View at Google Scholar · View at Scopus
  125. E. Puxeddu, N. Mitsutake, J. A. Knauf et al., “Microsomal prostaglandin E2 synthase-1 is induced by conditional expression of RET/PTC in thyroid PCCL3 cells through the activation of the MEK-ERK pathway,” The Journal of Biological Chemistry, vol. 278, no. 52, pp. 52131–52138, 2003. View at Publisher · View at Google Scholar · View at Scopus
  126. M. G. Borrello, L. Alberti, A. Fischer et al., “Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 41, pp. 14825–14830, 2005. View at Publisher · View at Google Scholar · View at Scopus
  127. R. M. Melillo, M. D. Castellone, V. Guarino et al., “The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells,” The Journal of Clinical Investigation, vol. 115, no. 4, pp. 1068–1081, 2005. View at Publisher · View at Google Scholar · View at Scopus
  128. J. P. Russell, S. Shinohara, R. M. Melillo, M. D. Castellone, M. Santoro, and J. L. Rothstein, “Tyrosine kinase oncoprotein, RET/PTC3, induces the secretion of myeloid growth and chemotactic factors,” Oncogene, vol. 22, no. 29, pp. 4569–4577, 2003. View at Publisher · View at Google Scholar · View at Scopus
  129. J. P. Russell, J. B. Engiles, and J. L. Rothstein, “Proinflammatory mediators and genetic background in oncogene mediated tumor progression,” Journal of Immunology, vol. 172, no. 7, pp. 4059–4067, 2004. View at Publisher · View at Google Scholar · View at Scopus
  130. R. M. Steinman and J. Banchereau, “Taking dendritic cells into medicine,” Nature, vol. 449, no. 7161, pp. 419–426, 2007. View at Publisher · View at Google Scholar · View at Scopus
  131. V. R. Yanofsky, H. Mitsui, D. Felsen, and J. A. Carucci, “Understanding dendritic cells and their role in cutaneous carcinoma and cancer immunotherapy,” Clinical and Developmental Immunology, vol. 2013, Article ID 624123, 14 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  132. K. Palucka and J. Banchereau, “Cancer immunotherapy via dendritic cells,” Nature Reviews Cancer, vol. 12, no. 4, pp. 265–277, 2012. View at Publisher · View at Google Scholar · View at Scopus
  133. S. K. Kim, K.-H. Song, S. D. Lim et al., “Clinical and pathological features and the BRAFV600E mutation in patients with papillary thyroid carcinoma with and without concurrent Hashimoto thyroiditis,” Thyroid, vol. 19, no. 2, pp. 137–141, 2009. View at Publisher · View at Google Scholar · View at Scopus
  134. H. Sumimoto, F. Imabayashi, T. Iwata, and Y. Kawakami, “The BRAF-MAPK signaling pathway is essential for cancer-immune evasion in human melanoma cells,” The Journal of Experimental Medicine, vol. 203, no. 7, pp. 1651–1656, 2006. View at Publisher · View at Google Scholar · View at Scopus
  135. S. Crawford, D. Belajic, J. Wei et al., “A novel B-RAF inhibitor blocks interleukin-8 (IL-8) synthesis in human melanoma xenografts, revealing IL-8 as a potential pharmacodynamic biomarker,” Molecular Cancer Therapeutics, vol. 7, no. 3, pp. 492–499, 2008. View at Publisher · View at Google Scholar · View at Scopus
  136. R. C. Smallridge, A.-M. Chindris, Y. W. Asmann et al., “RNA sequencing identifies multiple fusion transcripts, differentially expressed genes, and reduced expression of immune function genes in BRAF (V600E) mutant vs BRAF wild-type papillary thyroid carcinoma,” Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 2, pp. E338–E347, 2014. View at Publisher · View at Google Scholar · View at Scopus
  137. W. L. Smith, E. A. Meade, and D. L. DeWitt, “Interactions of PGH synthase isozymes-1 and -2 with NSAIDs,” Annals of the New York Academy of Sciences, vol. 744, pp. 50–57, 1994. View at Publisher · View at Google Scholar · View at Scopus
  138. J. L. Masferrer, K. M. Leahy, A. T. Koki et al., “Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors,” Cancer Research, vol. 60, no. 5, pp. 1306–1311, 2000. View at Google Scholar · View at Scopus
  139. H. Fujita, K. Koshida, E. T. Keller et al., “Cyclooxygenase-2 promotes prostate cancer progression,” Prostate, vol. 53, no. 3, pp. 232–240, 2002. View at Publisher · View at Google Scholar · View at Scopus
  140. J. Krishnan, V. Kirkin, A. Steffen et al., “Differential in vivo and in vitro expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in tumors and its relationship to lymphatic metastasis in immunocompetent rats,” Cancer Research, vol. 63, no. 3, pp. 713–722, 2003. View at Google Scholar · View at Scopus
  141. M. A. Molina, M. Sitja-Arnau, M. G. Lemoine, M. L. Frazier, and F. A. Sinicrope, “Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs,” Cancer Research, vol. 59, no. 17, pp. 4356–4362, 1999. View at Google Scholar · View at Scopus
  142. R. Talar-Wojnarowska, A. Gasiorowska, M. Olakowski et al., “Role of cyclooxygenase-2 gene polymorphisms in pancreatic carcinogenesis,” World Journal of Gastroenterology, vol. 17, no. 36, pp. 4113–4117, 2011. View at Publisher · View at Google Scholar · View at Scopus
  143. W. K. Leung, K. F. To, M. Y. Y. Go et al., “Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma.,” International journal of oncology, vol. 23, no. 5, pp. 1317–1322, 2003. View at Google Scholar · View at Scopus
  144. N. O. Lee, J.-W. Park, J. A. Lee et al., “Dual action of a selective cyclooxygenase-2 inhibitor on vascular endothelial growth factor expression in human hepatocellular carcinoma cells: novel involvement of discoidin domain receptor 2,” Journal of Cancer Research and Clinical Oncology, vol. 138, no. 1, pp. 73–84, 2012. View at Publisher · View at Google Scholar · View at Scopus
  145. Y. Ota, T. Imai, M. Hasumura et al., “Prostaglandin synthases influence thyroid follicular cell proliferation but not carcinogenesis in rats initiated with N-Bis(2-hydroxypropyl)nitrosamine,” Toxicological Sciences, vol. 127, no. 2, pp. 339–347, 2012. View at Publisher · View at Google Scholar · View at Scopus
  146. K. J. Lee, Y. S. Jung, W. H. Kim, T. I. Yoon, H. J. Joo, and E. Y. Soh, “Cyclooxygenase-2 expression in human thyroid disease,” Journal of Endocrinological Investigation, vol. 31, no. 2, pp. 111–118, 2008. View at Publisher · View at Google Scholar · View at Scopus
  147. B. Ji, Y. Liu, P. Zhang, Y. Wang, and G. Wang, “COX-2 expression and tumor angiogenesis in thyroid carcinoma patients among northeast Chinese population-result of a single-center study,” International Journal of Medical Sciences, vol. 9, no. 3, pp. 237–242, 2012. View at Publisher · View at Google Scholar · View at Scopus
  148. P. Siironen, A. Ristimäki, K. Narko et al., “VEGF-C and COX-2 expression in papillary thyroid cancer,” Endocrine-Related Cancer, vol. 13, no. 2, pp. 465–473, 2006. View at Publisher · View at Google Scholar · View at Scopus
  149. A. J. Cornetta, J. P. Russell, M. Cunnane, W. M. Keane, and J. L. Rothstein, “Cyclooxygenase-2 expression in human thyroid carcinoma and Hashimoto's thyroiditis,” Laryngoscope, vol. 112, no. 2, pp. 238–242, 2002. View at Publisher · View at Google Scholar · View at Scopus
  150. Y. Ito, H. Yoshida, K. Nakano et al., “Cyclooxygenase-2 expression in thyroid neoplasms,” Histopathology, vol. 42, no. 5, pp. 492–497, 2003. View at Publisher · View at Google Scholar · View at Scopus
  151. D.-J. Lim, K.-H. Baek, Y.-S. Lee et al., “Clinical, histopathological, and molecular characteristics of papillary thyroid microcarcinoma,” Thyroid, vol. 17, no. 9, pp. 883–888, 2007. View at Publisher · View at Google Scholar · View at Scopus
  152. S. Kajita, K. H. Ruebel, M. B. Casey, N. Nakamura, and R. V. Lloyd, “Role of COX-2, thromboxane A2 synthase, and prostaglandin I2 synthase in papillary thyroid carcinoma growth,” Modern Pathology, vol. 18, no. 2, pp. 221–227, 2005. View at Publisher · View at Google Scholar · View at Scopus
  153. S. Scarpino, E. Duranti, A. Stoppacciaro et al., “COX-2 is induced by HGF stimulation in Met-positive thyroid papillary carcinoma cells and is involved in tumour invasiveness,” Journal of Pathology, vol. 218, no. 4, pp. 487–494, 2009. View at Publisher · View at Google Scholar · View at Scopus
  154. K. O. Franssila, “Prognosis in thyroid carcinoma,” Cancer, vol. 36, no. 3, pp. 1138–1146, 1975. View at Publisher · View at Google Scholar · View at Scopus
  155. T. Enomoto, H. Sugawa, D. Inoue et al., “Establishment of human undifferentiated thyroid cancer cell line producing several growth factors and cytokines,” Cancer, vol. 65, no. 9, pp. 1971–1979, 1990. View at Publisher · View at Google Scholar · View at Scopus
  156. H. Murabe, T. Akamizu, A. Kubota, and S. Kusaka, “Anaplastic thyroid carcinoma with prominent cardiac metastasis, accompanied by a marked leukocytosis with a neutrophilia and high GM-CSF level in serum,” Internal Medicine, vol. 31, no. 9, pp. 1107–1111, 1992. View at Publisher · View at Google Scholar · View at Scopus
  157. T. Sato, M. Omura, J. Saito et al., “Neutrophilia associated with anaplastic carcinoma of the thyroid: production of macrophage colony-stimulating factor (M-CSF) and interleukin-6,” Thyroid, vol. 10, no. 12, pp. 1113–1118, 2000. View at Publisher · View at Google Scholar · View at Scopus
  158. S. Suzuki, M. Shibata, K. Gonda et al., “Immunosuppression involving increased myeloid-derived suppressor cell levels, systemic inflammation and hypoalbuminemia are present in patients with anaplastic thyroid cancer,” Molecular Clinical Oncology, vol. 1, no. 6, pp. 959–964, 2013. View at Google Scholar
  159. Y. Liu and G. Zeng, “Cancer and innate immune system interactions: translational potentials for cancer immunotherapy,” Journal of Immunotherapy, vol. 35, no. 4, pp. 299–308, 2012. View at Publisher · View at Google Scholar · View at Scopus
  160. T. F. Gajewski, M. B. Fuertes, and S. R. Woo, “Innate immune sensing of cancer: Clues from an identified role for type I IFNs,” Cancer Immunology, Immunotherapy, vol. 61, no. 8, pp. 1343–1347, 2012. View at Publisher · View at Google Scholar · View at Scopus
  161. L. Apetoh, F. Ghiringhelli, A. Tesniere et al., “Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy,” Nature Medicine, vol. 13, no. 9, pp. 1050–1059, 2007. View at Publisher · View at Google Scholar · View at Scopus
  162. K. Chen, J. Huang, W. Gong, P. Iribarren, N. M. Dunlop, and J. M. Wang, “Toll-like receptors in inflammation, infection and cancer,” International Immunopharmacology, vol. 7, no. 10, pp. 1271–1285, 2007. View at Publisher · View at Google Scholar · View at Scopus
  163. J. Kluwe, A. Mencin, and R. F. Schwabe, “Toll-like receptors, wound healing, and carcinogenesis,” Journal of Molecular Medicine, vol. 87, no. 2, pp. 125–138, 2009. View at Publisher · View at Google Scholar · View at Scopus
  164. S. Rakoff-Nahoum and R. Medzhitov, “Toll-like receptors and cancer,” Nature Reviews Cancer, vol. 9, no. 1, pp. 57–63, 2009. View at Publisher · View at Google Scholar · View at Scopus
  165. M. Nishimura and S. Naito, “Tissue-specific mRNA expression profiles of human toll-like receptors and related genes,” Biological and Pharmaceutical Bulletin, vol. 28, no. 5, pp. 886–892, 2005. View at Publisher · View at Google Scholar · View at Scopus
  166. J. P. Nicola, M. L. Vélez, A. M. Lucero, L. Fozzatti, C. G. Pellizas, and A. M. Masini-Repiso, “Functional Toll-like receptor 4 conferring lipopolysaccharide responsiveness is expressed in thyroid cells,” Endocrinology, vol. 150, no. 1, pp. 500–508, 2009. View at Publisher · View at Google Scholar · View at Scopus
  167. M. Voulgarelis and S. Ioannou, “Toll-like receptors, tissue injury, and tumourigenesis,” Mediators of Inflammation, vol. 2010, Article ID 581837, 9 pages, 2010. View at Publisher · View at Google Scholar · View at Scopus
  168. A. Dardano, R. Rizzo, A. Polini et al., “Soluble human leukocyte antigen-g and its insertion/deletion polymorphism in papillary thyroid carcinoma: novel potential biomarkers of disease?” The Journal of Clinical Endocrinology & Metabolism, vol. 97, no. 11, pp. 4080–4086, 2012. View at Publisher · View at Google Scholar · View at Scopus
  169. L. M. Nunes, F. M. Ayres, I. C. M. Francescantonio et al., “Association between the HLA-G molecule and lymph node metastasis in papillary thyroid cancer,” Human Immunology, vol. 74, no. 4, pp. 447–451, 2013. View at Publisher · View at Google Scholar · View at Scopus
  170. G. Trinchieri, “Biology of natural killer cells,” Advances in Immunology, vol. 47, pp. 187–376, 1989. View at Publisher · View at Google Scholar · View at Scopus
  171. 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
  172. E. Vivier, D. H. Raulet, A. Moretta et al., “Innate or adaptive immunity? The example of natural killer cells,” Science, vol. 331, no. 6013, pp. 44–49, 2011. View at Publisher · View at Google Scholar · View at Scopus
  173. F. Gogali, G. Paterakis, G. Z. Rassidakis et al., “Phenotypical analysis of lymphocytes with suppressive and regulatory properties (Tregs) and NK cells in the papillary carcinoma of thyroid,” The Journal of Clinical Endocrinology & Metabolism, vol. 97, no. 5, pp. 1474–1482, 2012. View at Publisher · View at Google Scholar · View at Scopus
  174. F. Gogali, G. Paterakis, G. Z. Rassidakis, C. I. Liakou, and C. Liapi, “CD3-CD16-CD56bright immunoregulatory NK cells are increased in the tumor microenvironment and inversely correlate with advanced stages in patients with papillary thyroid cancer,” Thyroid, vol. 23, no. 12, pp. 1561–1568, 2013. View at Publisher · View at Google Scholar · View at Scopus
  175. M. A. Cooper, T. A. Fehniger, S. C. Turner et al., “Human natural killer cells: a unique innate immunoregulatory role for the CD56bright subset,” Blood, vol. 97, no. 10, pp. 3146–3151, 2001. View at Publisher · View at Google Scholar · View at Scopus
  176. D. M. Baume, M. J. Robertson, H. Levine, T. J. Manley, P. W. Schow, and J. Ritz, “Differential responses to interleukin 2 define functionally distinct subsets of human natural killer cells,” European Journal of Immunology, vol. 22, no. 1, pp. 1–6, 1992. View at Publisher · View at Google Scholar · View at Scopus
  177. K. Tsuge, H. Takeda, S. Kawada, K. Maeda, and M. Yamakawa, “Characterization of dendritic cells in differentiated thyroid cancer,” Journal of Pathology, vol. 205, no. 5, pp. 565–576, 2005. View at Publisher · View at Google Scholar · View at Scopus
  178. C. Ugolini, F. Basolo, A. Proietti et al., “Lymphocyte and immature dendritic cell infiltrates in differentiated, poorly differentiated, and undifferentiated thyroid carcinoma,” Thyroid, vol. 17, no. 5, pp. 389–393, 2007. View at Publisher · View at Google Scholar · View at Scopus
  179. O. Hilly, R. Koren, R. Raz et al., “The role of S100-positive dendritic cells in the prognosis of papillary thyroid carcinoma,” American Journal of Clinical Pathology, vol. 139, no. 1, pp. 87–92, 2013. View at Publisher · View at Google Scholar · View at Scopus
  180. M. P. Pusztaszeri, P. M. Sadow, and W. C. Faquin, “Association of cd1a-positive dendritic cells with papillary thyroid carcinoma in thyroid fine-needle aspirations: a cytologic and immunocytochemical evaluation,” Cancer Cytopathology, vol. 121, no. 4, pp. 206–213, 2013. View at Publisher · View at Google Scholar · View at Scopus
  181. A. Proietti, C. Ugolini, R. M. Melillo et al., “Higher intratumoral expression of CD1a, tryptase, and CD68 in a follicular variant of papillary thyroid carcinoma compared to adenomas: correlation with clinical and pathological parameters,” Thyroid, vol. 21, no. 11, pp. 1209–1215, 2011. View at Publisher · View at Google Scholar · View at Scopus
  182. S. Scarpino, A. Stoppacciaro, F. Ballerini et al., “Papillary carcinoma of the thyroid: hepatocyte growth factor (HGF) stimulates tumor cells to release chemokines active in recruiting dendritic cells,” The American Journal of Pathology, vol. 156, no. 3, pp. 831–837, 2000. View at Publisher · View at Google Scholar · View at Scopus
  183. S. Scarpino, A. Stoppacciaro, C. Colarossi et al., “Hepatocyte growth factor (HGF) stimulates tumour invasiveness in papillary carcinoma of the thyroid,” The Journal of Pathology, vol. 189, no. 4, pp. 570–575, 1999. View at Google Scholar
  184. L. P. Ruco, T. Ranalli, A. Marzullo et al., “Expression of Met protein in thyroid tumours,” Journal of Pathology, vol. 180, no. 3, pp. 266–270, 1996. View at Google Scholar
  185. A. Zanetti, A. Stoppacciaro, A. Marzullo et al., “Expression of Met protein and urokinase-type plasminogen activator receptor (uPA-R) in papillary carcinoma of the thyroid,” The Journal of Pathology, vol. 186, no. 3, pp. 287–291, 1998. View at Google Scholar
  186. J. J. Costa, P. F. Weller, and S. J. Galli, “The cells of the allergic response: mast cells, basophils, and eosinophils,” The Journal of the American Medical Association, vol. 278, no. 22, pp. 1815–1822, 1997. View at Publisher · View at Google Scholar · View at Scopus
  187. M. Taweevisit, “The association of stromal mast cell response and tumor cell differentiation in colorectal cancer,” Journal of the Medical Association of Thailand, vol. 89, supplement 3, pp. S69–S73, 2006. View at Google Scholar · View at Scopus
  188. T. W. Beer, L. B. Ng, and K. Murray, “Mast cells have prognostic value in Merkel cell carcinoma,” American Journal of Dermatopathology, vol. 30, no. 1, pp. 27–30, 2008. View at Publisher · View at Google Scholar · View at Scopus
  189. R. M. Melillo, V. Guarino, E. Avilla et al., “Mast cells have a protumorigenic role in human thyroid cancer,” Oncogene, vol. 29, no. 47, pp. 6203–6215, 2010. View at Publisher · View at Google Scholar · View at Scopus
  190. M. F. Acikalin, Ü. Öner, I. Topçu, B. Yaşar, H. Kiper, and E. Çolak, “Tumour angiogenesis and mast cell density in the prognostic assessment of colorectal carcinomas,” Digestive and Liver Disease, vol. 37, no. 3, pp. 162–169, 2005. View at Publisher · View at Google Scholar · View at Scopus
  191. B. Caillou, M. Talbot, U. Weyemi et al., “Tumor-Associated macrophages (TAMs) form an interconnected cellular supportive network in anaplastic thyroid carcinoma,” PLoS ONE, vol. 6, no. 7, Article ID e22567, 2011. View at Publisher · View at Google Scholar · View at Scopus
  192. A. Mantovani, S. Sozzani, M. Locati, P. Allavena, and A. Sica, “Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes,” Trends in Immunology, vol. 23, no. 11, pp. 549–555, 2002. View at Publisher · View at Google Scholar · View at Scopus
  193. G. Herrmann, P.-M. Schumm-Draeger, C. Müller et al., “T lymphocytes, CD68-positive cells and vascularisation in thyroid carcinomas,” Journal of Cancer Research and Clinical Oncology, vol. 120, no. 11, pp. 651–656, 1994. View at Publisher · View at Google Scholar · View at Scopus
  194. M. Ryder, R. A. Ghossein, J. C. M. Ricarte-Filho, J. A. Knauf, and J. A. Fagin, “Increased density of tumor-associated macrophages is associated with decreased survival in advanced thyroid cancer,” Endocrine-Related Cancer, vol. 15, no. 4, pp. 1069–1074, 2008. View at Publisher · View at Google Scholar · View at Scopus
  195. M. Ryder, M. Gild, T. M. Hohl et al., “Genetic and pharmacological targeting of CSF-1/CSF-1R inhibits tumor-associated macrophages and impairs BRAF-induced thyroid cancer progression,” PLoS ONE, vol. 8, no. 1, Article ID e54302, 2013. View at Publisher · View at Google Scholar · View at Scopus
  196. L. L. Cunha, E. C. Morari, A. C. T. Guihen et al., “Infiltration of a mixture of immune cells may be related to good prognosis in patients with differentiated thyroid carcinoma,” Clinical Endocrinology, vol. 77, no. 6, pp. 918–925, 2012. View at Publisher · View at Google Scholar · View at Scopus
  197. A. Fiumara, A. Belfiore, G. Russo et al., “In situ evidence of neoplastic cell phagocytosis by macrophages in papillary thyroid cancer,” Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 5, pp. 1615–1620, 1997. View at Google Scholar · View at Scopus
  198. C. Janeway, Immunobiology: The Immune System in Health and Disease, Garland Science, New York, NY, USA, 6th edition, 2005.
  199. B. Alberts, Molecular Biology of the Cell, Garland Science, New York, NY, USA, 5th edition, 2008.
  200. D. G. Villagelin, R. B. Santos, and J. H. Romaldini, “Is diffuse and peritumoral lymphocyte infiltration in papillary thyroid cancer a marker of good prognosis?” Journal of Endocrinological Investigation, vol. 34, no. 11, pp. e403–e408, 2011. View at Google Scholar · View at Scopus
  201. G. Zhou and H. I. Levitsky, “Natural regulatory T cells and de novo-induced regulatory T cells contribute independently to tumor-specific tolerance,” The Journal of Immunology, vol. 178, no. 4, pp. 2155–2162, 2007. View at Publisher · View at Google Scholar · View at Scopus
  202. X. Su, J. Ye, E. C. Hsueh, Y. Zhang, D. F. Hoft, and G. Peng, “Tumor microenvironments direct the recruitment and expansion of human Th17 cells,” Journal of Immunology, vol. 184, no. 3, pp. 1630–1641, 2010. View at Publisher · View at Google Scholar · View at Scopus
  203. S. Moretti, E. Menicali, P. Voce et al., “Indoleamine 2,3-Dioxygenase 1 (IDO1) is up-regulated in thyroid carcinoma and drives the development of an immunosuppressant tumor microenvironment,” Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 5, pp. E832–E840, 2014. View at Publisher · View at Google Scholar · View at Scopus
  204. S. D. Larson, L. N. Jackson, T. S. Riall et al., “Increased incidence of well-differentiated thyroid cancer associated with Hashimoto thyroiditis and the role of the PI3k/Akt pathway,” Journal of the American College of Surgeons, vol. 204, no. 5, pp. 764–773, 2007. View at Publisher · View at Google Scholar · View at Scopus
  205. D. El Demellawy, A. Nasr, and S. Alowami, “Application of CD56, P63 and CK19 immunohistochemistry in the diagnosis of papillary carcinoma of the thyroid,” Diagnostic Pathology, vol. 3, no. 1, 2008. View at Publisher · View at Google Scholar · View at Scopus
  206. E. C. Morari, J. R. Silva, A. C. T. Guilhen et al., “Muc-1 expression may help characterize thyroid nodules but does not predict patients' outcome,” Endocrine Pathology, vol. 21, no. 4, pp. 242–249, 2010. View at Publisher · View at Google Scholar · View at Scopus
  207. L. L. Cunha, E. C. Morari, A. C. Guihen et al., “Infiltration of a mixture of different immune cells may be related to molecular profile of differentiated thyroid cancer,” Endocrine Related Cancer, vol. 19, no. 3, pp. L31–L36, 2012. View at Publisher · View at Google Scholar · View at Scopus
  208. J. Hamanishi, M. Mandai, M. Iwasaki et al., “Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 9, pp. 3360–3365, 2007. View at Publisher · View at Google Scholar · View at Scopus
  209. R. H. Thompson, S. M. Kuntz, B. C. Leibovich et al., “Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up,” Cancer Research, vol. 66, no. 7, pp. 3381–3385, 2006. View at Publisher · View at Google Scholar · View at Scopus
  210. L. L. Cunha, M. A. Marcello, E. C. Morari et al., “Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation,” Endocrine-Related Cancer, vol. 20, no. 1, pp. 103–110, 2013. View at Publisher · View at Google Scholar · View at Scopus
  211. J. D. French, G. R. Kotnis, S. Said et al., “Programmed death-1+ T cells and regulatory T cells are enriched in tumor-involved lymph nodes and associated with aggressive features in papillary thyroid cancer,” Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 6, pp. E934–E943, 2012. View at Publisher · View at Google Scholar · View at Scopus
  212. E. Kebebew, P. H. Ituarte, A. E. Siperstein, Q. Y. Duh, and O. H. Clark, “Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems,” Cancer, vol. 88, no. 5, pp. 1139–1148, 2000. View at Google Scholar
  213. M. Simbolo, C. Mian, S. Barollo et al., “High-throughput mutation profiling improves diagnostic stratification of sporadic medullary thyroid carcinomas,” Virchows Archiv, vol. 465, no. 1, pp. 73–78, 2014. View at Publisher · View at Google Scholar · View at Scopus
  214. G. W. Krampitz and J. A. Norton, “RET gene mutations (genotype and phenotype) of multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma,” Cancer, vol. 120, no. 13, pp. 1920–1931, 2014. View at Publisher · View at Google Scholar · View at Scopus
  215. H. Ma, Y. Ke, Q. Li, and J. A. Kapp, “Bovine and human insulin activate CD8+-autoreactive CTL expressing both type 1 and type 2 cytokines in C57BL/6 mice,” Journal of Immunology, vol. 164, no. 1, pp. 86–92, 2000. View at Publisher · View at Google Scholar · View at Scopus
  216. K. Kimura, T. Kawamura, S. Kadotani, H. Inada, S. Niihira, and T. Yamano, “Peptide-specific cytotoxicity of T lymphocytes against glutamic acid decarboxylase and insulin in type 1 diabetes mellitus,” Diabetes Research and Clinical Practice, vol. 51, no. 3, pp. 173–179, 2001. View at Publisher · View at Google Scholar · View at Scopus
  217. M. Nakayama, N. Abiru, H. Moriyama et al., “Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice,” Nature, vol. 435, no. 7039, pp. 220–223, 2005. View at Publisher · View at Google Scholar · View at Scopus
  218. R. E. Rocklin, R. Gagel, Z. Feldman, and A. H. Tashjian Jr., “Cellular immune responses in familial medullary thyroid carcinoma,” The New England Journal of Medicine, vol. 296, no. 15, pp. 835–838, 1977. View at Publisher · View at Google Scholar · View at Scopus
  219. J. M. George, M. A. Williams, R. Almoney, and G. Sizemore, “Medullary carcinoma of the thyroid. Cellular immune response to tumor antigen in a heritable human cancer,” Cancer, vol. 36, no. 5, pp. 1658–1661, 1975. View at Publisher · View at Google Scholar · View at Scopus
  220. S. Müller, D. Poehnert, J. A. Müller, G. W. F. Scheumann, M. Koch, and R. Lück, “Regulatory T cells in peripheral blood, lymph node, and thyroid tissue in patients with medullary thyroid carcinoma,” World Journal of Surgery, vol. 34, no. 7, pp. 1481–1487, 2010. View at Publisher · View at Google Scholar · View at Scopus
  221. R. Zhang, N. Scherberg, and L. J. DeGroot, “Monoclonal antibodies to rat calcitonin: their use in antigenic mapping and immunohistochemistry,” Endocrinology, vol. 138, no. 4, pp. 1691–1696, 1997. View at Publisher · View at Google Scholar · View at Scopus
  222. K. Haupt, F. Siegel, M. Lu et al., “Induction of a cellular and humoral immune response against preprocalcitonin by genetic immunization: a potential new treatment for medullary thyroid carcinoma,” Endocrinology, vol. 142, no. 3, pp. 1017–1023, 2001. View at Publisher · View at Google Scholar · View at Scopus
  223. M. Wuttke, C. Papewalis, Y. Meyer et al., “Amino acid-modified calcitonin immunization induces tumor epitope-specific immunity in a transgenic mouse model for medullary thyroid carcinoma,” Endocrinology, vol. 149, no. 11, pp. 5627–5634, 2008. View at Publisher · View at Google Scholar · View at Scopus
  224. M. Schott, “Immunesurveillance by dendritic cells: potential implication for immunotherapy of endocrine cancers,” Endocrine-Related Cancer, vol. 13, no. 3, pp. 779–795, 2006. View at Publisher · View at Google Scholar · View at Scopus
  225. M. Schott, J. Seissler, M. Lettmann, V. Fouxon, W. A. Scherbaum, and J. Feldkamp, “Immunotherapy for medullary thyroid carcinoma by dendritic cell vaccination,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 10, pp. 4965–4969, 2001. View at Publisher · View at Google Scholar · View at Scopus
  226. M. Schott, J. Feldkamp, M. Klucken, G. Kobbe, W. A. Scherbaum, and J. Seissler, “Calcitonin-specific antitumor immunity in medullary thyroid carcinoma following dendritic cell vaccination,” Cancer Immunology, Immunotherapy, vol. 51, no. 11-12, pp. 663–668, 2002. View at Publisher · View at Google Scholar · View at Scopus
  227. A. Stift, M. Sachet, R. Yagubian et al., “Dendritic cell vaccination in medullary thyroid carcinoma,” Clinical Cancer Research, vol. 10, no. 9, pp. 2944–2953, 2004. View at Publisher · View at Google Scholar · View at Scopus
  228. T. Bachleitner-Hofmann, J. Friedl, M. Hassler et al., “Pilot trial of autologous dendritic cells loaded with tumor lysate(s) from allogeneic tumor cell lines in patients with metastatic medullary thyroid carcinoma,” Oncology Reports, vol. 21, no. 6, pp. 1585–1592, 2009. View at Publisher · View at Google Scholar · View at Scopus
  229. N. Amino, T. Pysher, E. P. Cohen, and L. J. Degroot, “Immunologic aspects of human thyroid cancer. Humoral and cell mediated immunity, and a trial of immunotherapy,” Cancer, vol. 36, no. 3, pp. 963–973, 1975. View at Publisher · View at Google Scholar · View at Scopus