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01.01.2015 | Original Article

Cytokine production in peripheral blood cells of patients with differentiated thyroid cancer: elevated Th2/Th9 cytokine production before and reduced Th2 cytokine production after radioactive iodine therapy

verfasst von: Snezana Zivancevic Simonovic, Olgica Mihaljevic, Ivana Majstorovic, Predrag Djurdjevic, Irena Kostic, Olivera Milosevic Djordjevic, Ljiljana Mijatovic Teodorovic

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 1/2015

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Abstract

Cytokines play a key role in the regulation of cells of the immune system and also have been implicated in the pathogenesis of malignant diseases. The aim of this study was to evaluate cytokine profiles in patients with differentiated thyroid cancer (DTC) before and 7 days after radioactive iodine (131-I) therapy. Cytokine levels were determined in supernatants obtained from phytohemagglutinin-stimulated whole blood cultures of 13 patients with DTC and 13 control subjects. The concentrations of selected cytokines: Th1—interferon gamma (IFN-γ), interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α); Th2—interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 13 (IL-13) and interleukin 10 (IL-10); Th9—interleukin-9 (IL-9); and Th17—interleukin 17 (IL-17A) were measured using multiplex cytokine detection systems for Human Th1/Th2/Th9/Th17/Th22. We have shown that peripheral blood cells of DTC patients produce significantly higher concentrations of Th2/Th9 cytokines (IL-5, IL-13 and IL-9) than control subjects. The 131-I therapy led to reduced secretion of Th2 cytokines (IL-4, IL-5 and IL-13). Despite this, the calculated cytokine ratios (Th1/Th2) in DTC patients before and 7 days after 131-I therapy were not different from those in healthy subjects. DTC patients have significantly higher concentrations of Th2/Th9 cytokines (IL-5, IL-13 and IL-9) than control subjects. There is no influence of hypothyroidism or stage of disease on cytokine production in DTC patients before 131-I therapy. The radioactive 131-I therapy leads to reduced secretion of Th2 cytokines (IL-4, IL-5 and IL-13). Additional studies are needed to determine the significance of these findings.

Davies L, Welch HG (2006) Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA 295:2164–2167PubMedCrossRef

Schlumberger M, Sherman SI (2012) Endocrine tumors: approach to the patient with advanced differentiated thyroid cancer. Eur J Endocrinol 166:5–11PubMedCrossRef

Cooper DS, Doherty GM, Haugen BR et al (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19:1167–1214PubMedCrossRef

Luster M, Clarke SE, Dietlein M et al (2008) Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 35:1941–1959PubMedCrossRef

Punnonen R, Teisala K, Kuoppala T et al (1998) Cytokine production profiles in the peritoneal fluids of patients with malignant or benign gynecologic tumors. Cancer 83:788–796PubMedCrossRef

Clerici M, Shearer GM, Clerici E (1998) Cytokine dysregulation in invasive cervical carcinoma and other human neoplasias: time to consider the TH1/TH2 paradigm. J Natl Cancer Inst 90:261–263PubMedCrossRef

Budhu A, Wang XW (2006) The role of cytokines in hepatocellular carcinoma. J Leukoc Biol 80:1197–1213PubMedCrossRef

Bodelon C, Polley MY, Kemp TJ et al (2013) Circulating levels of immune and inflammatory markers and long versus short survival in early-stage lung cancer. Ann Oncol 24:2073–2079PubMedCentralPubMedCrossRef

Ellyard JI, Simson L, Parish CR (2007) Th2-mediated anti-tumour immunity: friend or foe? Tissue Antigens 70(1):1–11PubMedCrossRef

10.

Baier PK, Wolff-Vorbeck G, Eggstein S et al (2005) Cytokine expression in colon carcinoma. Anticancer Res 25:2135–2139PubMed

11.

Mocellin S, Provenzano M, Rossi CR et al (2003) Use of quantitative real-time PCR to determine immune cell density and cytokine gene profile in the tumor microenvironment. J Immunol Methods 280:1–11PubMedCrossRef

12.

Ikeguchi M, Matsumoto S, Murakami D et al (2004) Gene expression levels of cytokines in peritoneal washings from patients with gastric cancer. Tumour Biol 25:117–121PubMedCrossRef

13.

Montero AJ, Diaz-Montero CM, Millikan RE et al (2009) Cytokines and angiogenic factors in patients with metastatic renal cell carcinoma treated with interferon: association of pretreatment serum levels with survival. Ann Oncol 20:1682–1687PubMedCrossRef

14.

Özata M, Ergun H, Öziflik G et al (2000) Effect of radioiodine therapy on several hematological and immune parameters in patients with differentiated thyroid carcinoma. Turk J Endocrinol Metab 2:45–50

15.

Mardente S, Lenti L, Lococo E et al (2005) Phenotypic and functional characterization of lymphocytes in autoimmune thyroiditis and in papillary carcinoma. Anticancer Res 25:2483–2488PubMed

16.

Xiang GA, Chen KY, Wang NH et al (2010) Immunological influence of iodine-125 implantation in patients with hepatocellular carcinoma resection. Nan Fang Yi Ke Da Xue Xue Bao 30:292–294PubMed

17.

Jones BM, Kwok CCH, Kung AWC (1999) Effect of radioactive iodine therapy on cytokine production in Graves’ disease: transient increases in interleukin-4 (IL-4), IL-6, IL-10, and tumor necrosis factor-α, with longer term increases in interferon-γ production. J Clin Endocrinol Metab 84:4106–4110PubMed

18.

Heney D, Whicher JT (1995) Factors affecting the measurement of cytokines in biological fluids: implications for their clinical measurement. Ann Clin Biochem 32:358–368PubMedCrossRef

19.

Akira S, Taga T, Kishimoto T (1993) Interleukin-6 in biology and medicine. Adv Immunol 54:1–78PubMedCrossRef

20.

Stassi G, Todaro M, Zerilli M et al (2003) Thyroid cancer resistance to chemotherapeutic drugs via autocrine production of interleukin-4 and interleukin-10. Cancer Res 63:6784–6790PubMed

21.

Bais AG, Beckmann I, Lindemans J et al (2005) A shift to a peripheral Th2-type cytokine pattern during the carcinogenesis of cervical cancer becomes manifest in CIN III lesions. J Clin Pathol 58:1096–1100PubMedCentralPubMedCrossRef

22.

Kulbe H, Chakravarty P, Leinster DA et al (2012) A dynamic inflammatory cytokine network in the human ovarian cancer microenvironment. Cancer Res 72:66–75PubMedCentralPubMedCrossRef

23.

Duramad P, McMahon CW, Hubbard A et al (2004) Flow cytometric detection of intracellular Th1/Th2 cytokines using whole blood: validation of immunologic biomarker for use in epidemiologic studies. Cancer Epidemiol Biomark Prev 13:1452–1458

24.

Ito N, Nakamura H, Metsugi H et al (2001) Dissociation between T helper type 1 and type 2 differentiation and cytokine production in tumor-infiltrating lymphocytes in patients with lung cancer. Surg Today 31:390–394PubMedCrossRef

25.

Disis ML (2010) Immune regulation of cancer. J Clin Oncol 28:4531–4538PubMedCentralPubMedCrossRef

26.

Nevala WK, Vachon CM, Leontovich AA et al (2009) Evidence of systemic Th2-driven chronic inflammation in patients with metastatic melanoma. Clin Cancer Res 15:1931–1939PubMedCentralPubMedCrossRef

27.

Smyth GP, Stapleton PP, Barden CB et al (2003) Renal cell carcinoma induces prostaglandin E2 and T-helper type 2 cytokine production in peripheral blood mononuclear cells. Ann Surg Oncol 10:455–462PubMedCrossRef

28.

Davis BP, Rothenberg ME (2014) Eosinophils and cancer. Cancer Immunol Res 2:1–8PubMedCrossRef

29.

Fujisawa T, Terada A, Atsuta J et al (1997) IL-5 as a strong secretagogue for human eosinophils. Int Arch Allergy Immunol 114:81–83PubMedCrossRef

30.

Gatault S, Legrand F, Delbeke M et al (2012) Involvement of eosinophils in the anti-tumor response. Cancer Immunol Immunother 61:1527–1534PubMedCrossRef

31.

Kataoka S, Konishi Y, Nishio Y et al (2004) Antitumor activity of eosinophils activated by IL-5 and eotaxin against hepatocellular carcinoma. DNA Cell Biol 23:549–560PubMedCrossRef

32.

Simson L, Ellyard JI, Dent LA et al (2007) Regulation of carcinogenesis by IL-5 and CCL11: a potential role for eosinophils in tumor immune surveillance. J Immunol 178:4222–4229PubMedCrossRef

33.

Mattes J, Hulett M, Xie W et al (2003) Immunotherapy of cytotoxic T cell-resistant tumors by T helper 2 cells: an eotaxin and STAT6-dependent process. J Exp Med 197:387–393PubMedCentralPubMedCrossRef

34.

Modesti A, Masuelli L, Modica A et al (1993) Ultrastructural evidence of the mechanisms responsible for interleukin-4-activated rejection of a spontaneous murine adenocarcinoma. Int J Cancer 53:988–993PubMedCrossRef

35.

Musiani P, Allione A, Modica A et al (1996) Role of neutrophils and lymphocytes in inhibition of a mouse mammary adenocarcinoma engineered to release IL-2, IL-4, IL-7, IL-10, IFN-alpha, IFN-gamma, and TNF-alpha. Lab Invest 74:146–157PubMed

36.

Tepper RI, Coffman RL, Leder P (1992) An eosinophil-dependent mechanism for the antitumor effect of interleukin-4. Science 257:548–551PubMedCrossRef

37.

Lebel-Binay S, Laguerre B, Quintin-Colonna F et al (1995) Experimental gene therapy of cancer using tumor cells engineered to secrete interleukin-13. Eur J Immunol 25:2340–2348PubMedCrossRef

38.

Terabe M, Matsui S, Noben-Trauth N et al (2000) NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol 1:515–520PubMedCrossRef

39.

Ma HL, Whitters MJ, Jacobson BA et al (2004) Tumor cells secreting IL-13 but not IL-13Ralpha2 fusion protein have reduced тumorigenicity in vivo. Int Immunol 16:1009–1017PubMedCrossRef

40.

Li H, Rostami A (2010) IL-9: basic biology, signaling pathways in CD4+ T cells and implications for autoimmunity. J Neuroimmune Pharmacol 5:198–209PubMedCrossRef

41.

Purwar R, Schlapbach C, Xiao S et al (2012) Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells. Nat Med 18:1248–1253PubMedCrossRef

42.

Valli E, Sterle HA, Méndez-Huergo S et al (2013) Regulatory T cells mediate immunosupression induced by experimental hypothyroidism (P1215). J Immunol 190:188.10 (abstract)

43.

Nieto P, Peñaloza H, Salazar F et al (2014) Gestational hypothyroidism in mice makes female offspring more resistant to pneumococcal pneumonia (MUC5P.869). J Immunol 192:134.12 (abstract)

44.

Botella-Carretero JI, Prados A, Manzano L et al (2005) The effects of thyroid hormones on circulating markers of cell-mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal. Eur J Endocrinol 153:223–230PubMedCrossRef

45.

Barsegian V, Müller SP, Horn PA et al (2011) Lymphocyte function following radioiodine therapy in patients with thyroid carcinoma. Nuklearmedizin 50:195–203PubMedCrossRef

Titel: Cytokine production in peripheral blood cells of patients with differentiated thyroid cancer: elevated Th2/Th9 cytokine production before and reduced Th2 cytokine production after radioactive iodine therapy
verfasst von: Snezana Zivancevic Simonovic
Olgica Mihaljevic
Ivana Majstorovic
Predrag Djurdjevic
Irena Kostic
Olivera Milosevic Djordjevic
Ljiljana Mijatovic Teodorovic
Publikationsdatum: 01.01.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 1/2015
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-014-1619-7

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Cytokine production in peripheral blood cells of patients with differentiated thyroid cancer: elevated Th2/Th9 cytokine production before and reduced Th2 cytokine production after radioactive iodine therapy

Abstract

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