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Analysis of regulatory T cells frequency in peripheral blood and tumor tissues in papillary thyroid carcinoma with and without Hashimoto’s thyroiditis

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Abstract

Purpose

Regulatory T cells (Treg) suppress the immune reaction. The aim of the present study was to investigate the clinicopathologic significance and roles of Treg in papillary thyroid carcinoma (PTC) patients with and without Hashimoto’s thyroiditis.

Methods

Flow cytometry was used to detect the percentage of CD4+CD25+CD127low/− Treg among CD4+ T cells in peripheral blood. FoxP3+ Treg were detected by immunohistochemistry in the tumor tissues.

Results

The percentage of CD4+CD25+CD127low/− Treg among CD4+ T cells was significantly higher in PTC patients than that in multinodular goiter (MNG) patients. There were large numbers of tumor-infiltrating FoxP3+ Treg in primary PTC and metastatic lymph nodes tissues; however, there was no FoxP3 expression in the MNG tissues. Higher percentage of Treg both in peripheral blood and tumor tissues was associated with extrathyroidal extension and lymph nodes metastasis. The percentage of CD4+CD25+CD127low/− Treg among CD4+ T cells in peripheral blood of PTC patients with Hashimoto’s thyroiditis (HT) was significantly lower, whereas the infiltration of FoxP3+ Treg in tissues of PTC with HT tended to be increased.

Conclusions

We concluded that the percentage of Treg increased in peripheral blood as well as in the tumor tissues of PTC patients compared with that of MNG patients. The high percentage of Treg was associated with aggressiveness. There may be a compensatory expansion of Treg at the sites of inflammation in tissues of PTC with HT contributing to the immune response suppression.

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References

  1. Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995 (see comments). Cancer. 1998;83(12):2638–48.

    Article  CAS  PubMed  Google Scholar 

  2. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006;295(18):2164–7. doi:10.1001/jama.295.18.2164.

    Article  CAS  PubMed  Google Scholar 

  3. Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994;97(5):418–28.

    Article  CAS  PubMed  Google Scholar 

  4. Schlumberger M, Lacroix L, Russo D, Filetti S, Bidart JM. Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients. Nat Clin Pract Endocrinol Metab. 2007;3(3):260–9. doi:10.1038/ncpendmet0449.

    Article  CAS  PubMed  Google Scholar 

  5. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol. 2005;6(4):345–52. doi:10.1038/ni1178.

    Article  CAS  PubMed  Google Scholar 

  6. Hartigan-O’Connor DJ, Poon C, Sinclair E, McCune JM. Human CD4+ regulatory T cells express lower levels of the IL-7 receptor alpha chain (CD127), allowing consistent identification and sorting of live cells. J Immunol Methods. 2007;319(1–2):41–52. doi:10.1016/j.jim.2006.10.008.

    Article  PubMed  Google Scholar 

  7. Bennaceur K, Chapman JA, Touraine JL, Portoukalian J. Immunosuppressive networks in the tumour environment and their effect in dendritic cells. Biochim Biophys Acta. 2009;1795(1):16–24. doi:10.1016/j.bbcan.2008.07.001.

    CAS  PubMed  Google Scholar 

  8. Shevach EM. Certified professionals: CD4(+)CD25(+) suppressor T cells. J Exp Med. 2001;193(11):F41–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G. Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J Exp Med. 2001;193(11):1303–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Piccirillo CA, Shevach EM. Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells. J Immunol. 2001;167(3):1137–40.

    Article  CAS  PubMed  Google Scholar 

  11. Baecher-Allan C, Anderson DE. Regulatory cells and human cancer. Semin Cancer Biol. 2006;16(2):98–105. doi:10.1016/j.semcancer.2005.11.003.

    Article  CAS  PubMed  Google Scholar 

  12. Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res. 2003;9(2):606–12.

    PubMed  Google Scholar 

  13. Liotta F, Gacci M, Frosali F, Querci V, Vittori G, Lapini A, et al. Frequency of regulatory T cells in peripheral blood and in tumour-infiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma. BJU Int. 2011;107(9):1500–6. doi:10.1111/j.1464-410X.2010.09555.x.

    Article  CAS  PubMed  Google Scholar 

  14. Maruyama T, Kono K, Mizukami Y, Kawaguchi Y, Mimura K, Watanabe M, et al. Distribution of Th17 cells and FoxP3(+) regulatory T cells in tumor-infiltrating lymphocytes, tumor-draining lymph nodes and peripheral blood lymphocytes in patients with gastric cancer. Cancer Sci. 2010;101(9):1947–54. doi:10.1111/j.1349-7006.2010.01624.x.

    Article  CAS  PubMed  Google Scholar 

  15. Anz D, Eiber S, Scholz C, Endres S, Kirchner T, Bourquin C, et al. In breast cancer, a high ratio of tumour-infiltrating intraepithelial CD8+ to FoxP3+ cells is characteristic for the medullary subtype. Histopathology. 2011;59(5):965–74. doi:10.1111/j.1365-2559.2011.04040.x.

    Article  PubMed  Google Scholar 

  16. Tao H, Mimura Y, Aoe K, Kobayashi S, Yamamoto H, Matsuda E, et al. Prognostic potential of FOXP3 expression in non-small cell lung cancer cells combined with tumor-infiltrating regulatory T cells. Lung Cancer. 2012;75(1):95–101. doi:10.1016/j.lungcan.2011.06.002.

    Article  PubMed  Google Scholar 

  17. Fu J, Xu D, Liu Z, Shi M, Zhao P, Fu B, et al. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology. 2007;132(7):2328–39. doi:10.1053/j.gastro.2007.03.102.

    Article  PubMed  Google Scholar 

  18. French JD, Weber ZJ, Fretwell DL, Said S, Klopper JP, Haugen BR. Tumor-associated lymphocytes and increased FoxP3+ regulatory T cell frequency correlate with more aggressive papillary thyroid cancer. J Clin Endocrinol Metab. 2010;95(5):2325–33. doi:10.1210/jc.2009-2564.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Wu SF, Huang Y, Hou JK, Yuan TT, Zhou CX, Zhang J, et al. The downregulation of onzin expression by PKCepsilon-ERK2 signaling and its potential role in AML cell differentiation. Leukemia. 2010;24(3):544–51. doi:10.1038/leu.2009.280.

    Article  CAS  PubMed  Google Scholar 

  20. Gogali F, Paterakis G, Rassidakis GZ, Kaltsas G, Liakou CI, Gousis P, et al. Phenotypical analysis of lymphocytes with suppressive and regulatory properties (Tregs) and NK cells in the papillary carcinoma of thyroid. J Clin Endocrinol Metab. 2012;97(5):1474–82. doi:10.1210/jc.2011-1838.

    Article  CAS  PubMed  Google Scholar 

  21. Yu H, Huang X, Liu X, Jin H, Zhang G, Zhang Q et al. Regulatory T cells and plasmacytoid dendritic cells contribute to the immune escape of papillary thyroid cancer coexisting with multinodular non-toxic goiter. Endocrine. 2012. doi:10.1007/s12020-012-9853-2.

  22. DeGroot LJ, Kaplan EL, McCormick M, Straus FH. Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab. 1990;71(2):414–24.

    Article  CAS  PubMed  Google Scholar 

  23. Tanaka K, Sonoo H, Hirono M, Ohkubo S, Nomura T, Ikeda M, et al. Retrospective analysis of predictive factors for recurrence after curatively resected papillary thyroid carcinoma. Surg Today. 2005;35(9):714–9. doi:10.1007/s00595-005-3021-8.

    Article  PubMed  Google Scholar 

  24. Kashima K, Yokoyama S, Noguchi S, Murakami N, Yamashita H, Watanabe S, et al. Chronic thyroiditis as a favorable prognostic factor in papillary thyroid carcinoma. Thyroid. 1998;8(3):197–202.

    Article  CAS  PubMed  Google Scholar 

  25. Huang BY, Hseuh C, Chao TC, Lin KJ, Lin JD. Well-differentiated thyroid carcinoma with concomitant Hashimoto’s thyroiditis present with less aggressive clinical stage and low recurrence. Endocr Pathol. 2011;22(3):144–9. doi:10.1007/s12022-011-9164-9.

    Article  PubMed  Google Scholar 

  26. Dvorkin S, Robenshtok E, Hirsch D, Strenov Y, Shimon I, Benbassat CA. Differentiated thyroid cancer is associated with less aggressive disease and better outcome in patients with coexisting Hashimotos thyroiditis. J Clin Endocrinol Metab. 2013;98(6):2409–14. doi:10.1210/jc.2013-1309.

    Article  CAS  PubMed  Google Scholar 

  27. Sugiyama H, Gyulai R, Toichi E, Garaczi E, Shimada S, Stevens SR, et al. Dysfunctional blood and target tissue CD4+CD25 high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. J Immunol. 2005;174(1):164–73.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Saruta M, Yu QT, Fleshner PR, Mantel PY, Schmidt-Weber CB, Banham AH, et al. Characterization of FOXP3+CD4+ regulatory T cells in Crohn’s disease. Clin Immunol. 2007;125(3):281–90. doi:10.1016/j.clim.2007.08.003.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Dr. Baocun Sun for providing tissue materials and Dr. Xiubao Ren for his technical assistance. This work was supported in part by Grant from the National Natural Science Foundation of China (31200574) and Tianjin Municipal Science and technology project (12JCQNJC07700).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Head and Neck Tumor, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin, 300060, People’s Republic of China

    Y. Liu, X. Yun, M. Gao, Y. Yu & X. Li

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  1. Y. Liu
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  2. X. Yun
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  3. M. Gao
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Correspondence to M. Gao or X. Li.

Additional information

Y. Liu and X. Yun contributed equally to this work.

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Liu, Y., Yun, X., Gao, M. et al. Analysis of regulatory T cells frequency in peripheral blood and tumor tissues in papillary thyroid carcinoma with and without Hashimoto’s thyroiditis. Clin Transl Oncol 17, 274–280 (2015). https://doi.org/10.1007/s12094-014-1222-6

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  • DOI: https://doi.org/10.1007/s12094-014-1222-6

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