Hostname: page-component-8448b6f56d-t5pn6 Total loading time: 0 Render date: 2024-04-24T08:24:23.267Z Has data issue: false hasContentIssue false

Serum cytokine profile of laryngeal squamous cell carcinoma patients

Published online by Cambridge University Press:  15 March 2017

J Sotirović*
Affiliation:
Department of Otorhinolaryngology, Military Medical Academy, Belgrade, Serbia
A Perić
Affiliation:
Department of Otorhinolaryngology, Military Medical Academy, Belgrade, Serbia
D Vojvodić
Affiliation:
Institute for Medical Research, Military Medical Academy, Belgrade, Serbia
N Baletić
Affiliation:
Department of Otorhinolaryngology, Military Medical Academy, Belgrade, Serbia
I Zaletel
Affiliation:
Institute of Histology and Embryology ‘Aleksandar Đ Kostic’, School of Medicine, University of Belgrade, Belgrade, Serbia
I Stanojević
Affiliation:
Institute for Medical Research, Military Medical Academy, Belgrade, Serbia
M Erdoglija
Affiliation:
Department of Otorhinolaryngology, Military Medical Academy, Belgrade, Serbia
M Milojević
Affiliation:
Department of Otorhinolaryngology, Military Medical Academy, Belgrade, Serbia
*
Address for correspondence: Dr J Sotirović, Kaplara Momčila Gavrića 2, 11000 Belgrade, Serbia Fax: +381 11 2666 164 E-mail: j.sotirovic@gmail.com

Abstract

Objectives:

This study aimed to evaluate serum cytokine concentrations in healthy individuals and laryngeal squamous cell carcinoma patients.

Methods:

A total of 59 laryngeal squamous cell carcinoma patients and 44 healthy controls were included. Multiplex analysis of interleukins 2, 4, 5, 6, 10, 12, 13 and 17 and interferon-gamma with respect to the presence of laryngeal carcinoma, tumour–node–metastasis T stage, nodal involvement and larynx subsite was performed.

Results:

Statistical analysis revealed no difference in serum cytokine levels between patients and healthy controls. The serum interleukin-12 concentration was significantly higher in patients with early (T1–2) than in those with late (T3–4) stage disease and without nodal involvement (p < 0.05). Serum interleukin-10 levels were significantly higher in T3–4 stage than in T1–2 stage patients (p < 0.05). Additionally, serum interleukin 10, 12 and 13 concentrations (p < 0.05) and interleukin-6 concentration (p < 0.01) were significantly higher in patients with T1–2 stage supraglottic vs glottic tumours.

Conclusion:

Serum cytokines level cannot be used as laryngeal squamous cell carcinoma markers. Progression from T1–2 to T3–4 stage is followed by decreased serum interleukin-12 levels and increased interleukin-10 levels. Nodal involvement is associated with lower serum interleukin-12 levels. In patients with early stage tumours, serum interleukin 6, 10, 12 and 13 concentrations are significantly higher in those with supraglottic vs glottic tumours.

Type
Main Articles
Copyright
Copyright © JLO (1984) Limited 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1 Wan, YY. Multi-tasking of helper T cells. Immunology 2010;130:166–71CrossRefGoogle ScholarPubMed
2 Yang, B, Kang, H, Fung, A, Zhao, H, Wang, T, Ma, D. The role of interleukin 17 in proliferation, angiogenesis, and metastasis. Mediators Inflamm 2014;2014:623759 CrossRefGoogle ScholarPubMed
3 Zhang, X, Weng, W, Xu, W, Wang, Y, Yu, W, Tang, X et al. Prognostic significance of interleukin 17 in cancer: a meta-analysis. Int J ClinExp Med 2014;7:3258–69Google ScholarPubMed
4 Candido, J, Hagemann, T. Cancer-related inflammation. J Clin Immunol 2013;33(suppl 1):S79–84CrossRefGoogle ScholarPubMed
5 Lin, WW, Karin, M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 2007;117:1175–83CrossRefGoogle ScholarPubMed
6 Becker, Y. Molecular immunological approaches to biotherapy of human cancers – a review, hypothesis and implications. Anticancer Res 2006;26:1113–14Google ScholarPubMed
7 Albers, AE, Strauss, L, Liao, T, Hoffmann, TK, Kaufmann, AM. T-cell tumor interaction directs the development of immunotherapies in head and neck cancer. Clin Dev Immunol 2010;2010:236378 CrossRefGoogle ScholarPubMed
8 Bleotu, C, Chifiriuc, MC, Grigore, R, Grancea, C, Popescu, CR, Anton, G et al. Investigation of Th1/Th2 cytokine profiles in patients with laryngo-pharyngeal, HPV-positive cancers. Eur Arch Otorhinolaryngol 2013;270:711–18CrossRefGoogle ScholarPubMed
9 Eyigor, M, Eyigor, H, Osma, U, Yilmaz, MD, Erin, N, Selcuk, OT et al. Analysis of serum cytokine levels in larynx squamous cell carcinoma and dysplasia patients. Iran J Immunol 2014;11:259–68Google ScholarPubMed
10 Günaydin, , Kesikli, SA, Kansu, E, Hoşal, . Identification of the peripheral blood levels of interleukin-12, interleukin-10, and transforming growth factor-β in patients with laryngeal squamous cell carcinoma. Head Neck 2012;34:393–7CrossRefGoogle ScholarPubMed
11 Edge, S, Byrd, DR, Compton, CC, Fritz, AG, Greene, FL, Trotti, A, eds. AJCC Cancer Staging Manual, 7th edn. New York: Springer; 2009 Google Scholar
12 Schilling, B, Halstead, ES, Schuler, P, Harasymczuk, M, Eqan, JE, Whiteside, TL. IRX-2, a novel immunotherapeutic, enhances and protects NK-cell functions in cancer patients. Cancer Immunol Immunother 2012;61:1395–405CrossRefGoogle ScholarPubMed
13 Vesely, MD, Kershaw, MH, Schreiber, RD, Smyth, MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol 2011;29:235–71CrossRefGoogle ScholarPubMed
14 Kim, HJ, Cantor, H. CD4 T-cell subset and tumor immunity: the helpful and the not-so-helpful. Cancer Immunol Res 2014;2:91–8CrossRefGoogle ScholarPubMed
15 Young, MR. Protective mechanisms of head and neck squamous cell carcinoma from immune assault. Head Neck 2006;28:462–70CrossRefGoogle ScholarPubMed
16 Müller-Hübenthal, B, Azemar, M, Lorenzen, D, Huber, M, Freudenberg, MA, Galanos, C et al. Tumour biology: tumour-associated inflammation versus antitumor immunity. Anticancer Res 2009;29:4795–806Google ScholarPubMed
17 Allen, CT, Judd, NP, Bui, JD, Uppaluri, R. The clinical implications of antitumor immunity in head and neck cancer. Laryngoscope 2012;122:144–57CrossRefGoogle ScholarPubMed
18 Millrud, CR, Hylander, T, Kumlien Georen, S, Kågedal, Å, Winqvist, O, Cardell, LO. Inverse immunological responses induced by allergic rhinitis and head and neck squamous cell carcinoma. PLoS One 2014;9:e86796 CrossRefGoogle ScholarPubMed
19 Hoffmann, TK, Sonkoly, E, Homey, B, Scheckenbach, K, Gwosdz, C, Bas, M et al. Aberrant cytokine expression in serum of patients with adenoid cystic carcinoma and squamous cell carcinoma of the head and neck. Head Neck 2007;29:472–8CrossRefGoogle ScholarPubMed
20 Hathaway, B, Landsittel, DP, Gooding, W, Whiteside, TL, Grandis, JR, Siegfried, JM et al. Multiplexed analysis of serum cytokines as biomarkers in squamous cell carcinoma of the head and neck. Laryngoscope 2005;115:522–7CrossRefGoogle ScholarPubMed
21 Jebreel, A, Mistry, D, Loke, D, Dunn, G, Hough, V, Oliver, K et al. Investigation of interleukin 10, 12 and 18 levels in patients with head and neck cancer. J Laryngol Otol 2007;121:246–52CrossRefGoogle Scholar
22 Lathers, DM, Achille, NJ, Young, MR. Incomplete Th2 skewing of cytokines in plasma of patients with squamous cell carcinoma of the head and neck. Hum Immunol 2003;64:1160–6CrossRefGoogle ScholarPubMed
23 Kaskas, NM, Moore-Medlin, T, McClure, GB, Ekshyyan, O, Vanchiere, A, Nathan, CA. Serum biomarkers in head and neck squamous cell cancer. JAMA Otolaryngol Head Neck Surg 2014;140:511 CrossRefGoogle ScholarPubMed
24 Pai, SI, Westra, WH. Molecular pathology of head and neck cancer: implications for diagnosis, prognosis and treatment. Annu Rev Pathol 2009;4:4970 CrossRefGoogle ScholarPubMed
25 Westra, WH. The changing face of head and neck cancer in the 21st century: The impact of HPV on the epidemiology and pathology of oral cancer. Head Neck Pathol 2009;3:7881 CrossRefGoogle ScholarPubMed
26 Melinceanu, L, Lerescu, L, Tucureanu, C, Caras, I, Pitica, R, Sarafoleanu, C et al. Serum perioperative profile of cytokine in patients with squamous cell carcinoma of the larynx. J Otolaryngol Head Neck Surg 2011;40:143–50Google ScholarPubMed
27 Green, VL, Michno, A, Green, J, Stafford, ND. Effect of treatment on systemic cytokines in head and neck squamous cell carcinoma patients. Results Immunol 2012;2:16 CrossRefGoogle Scholar
28 Zundler, S, Neurath, MF. Interleukin-12: Functional activities and implications for disease. Cytokine Growth Factor Rev 2015;26:559–68CrossRefGoogle ScholarPubMed
29 Sorensen, EW, Gerber, SA, Frelinger, JG, Lord, EM. IL-12 suppresses vascular endothelial growth factor receptor 3 expression on tumor vessels by two distinct IFN-γ–dependent mechanisms. J Immunol 2010;184:1858–66CrossRefGoogle ScholarPubMed
30 Liang, W, Wang, XF. In vitro induction of specific anti-tumoral immunity against laryngeal carcinoma by using human interleukin-12 gene-transfected dendritic cells. Chin Med J (Engl) 2011;124:1357–61Google ScholarPubMed
31 Tian, L, Chen, X, Sun, Y, Liu, M, Zhu, D, Ren, J. Growth suppression of human laryngeal squamous cell carcinoma by adenoviral-mediated interleukin-12. J Int Med Res 2010;38:9941004 CrossRefGoogle ScholarPubMed
32 Geginat, J, Larghi, P, Paroni, M, Nizzoli, G, Penatti, A, Pagani, M et al. The light and the dark sides of Interleukin-10 in immune-mediated diseases and cancer. Cytokine Growth Factor Rev 2016;30:8793 CrossRefGoogle ScholarPubMed
33 Zhou, J, Zhang, D, Chen, B, Li, Q, Zhou, L, Liu, F et al. Association of interleukin-10 promoter polymorphisms and corresponding plasma levels with susceptibility to laryngeal squamous cell carcinoma. Oncol Lett 2014;7:1721–7CrossRefGoogle ScholarPubMed
34 Qian, X, Chen, H, Wu, X, Hu, L, Huang, Q, Jin, Y. Interleukin-17 acts as double-edged sword in anti-tumor immunity and tumorigenesis. Cytokine 2017;89:3444 CrossRefGoogle ScholarPubMed
35 Meng, CD, Zhu, DD, Jiang, XD, Li, L, Sha, JC, Dong, Z et al. Overexpression of interleukin-l7 in tumor-associated macrophages is correlated with the differentiation and angiogenesis of laryngeal squamous cell carcinoma. Chin Med J (Engl) 2012;125:1603–7Google ScholarPubMed
36 Kopta, R, Mochocki, M, Morawski, P, Brzezińska-Blaszczyk, E, Lewy-Trenda, I, Student Scientific Circle et al. Expression of Th17 cell population regulatory cytokines in laryngeal carcinoma – preliminary study. Contemp Oncol (Pozn) 2015;19:195200 Google ScholarPubMed
37 Mor, N, Blitzer, A. Functional anatomy and oncologic barriers of the larynx. Otolaryngol Clin North Am 2015;48:533–45CrossRefGoogle ScholarPubMed
38 Ozdek, A, Sarac, S, Akyol, MU, Unal, OF, Sungur, A. Histopathological predictors of occult lymph node metastases in supraglottic squamous cell carcinomas. Eur Arch Otorhinolaryngol 2000;257:389–92CrossRefGoogle ScholarPubMed
39 Nikakhlagh, S, Ranjbari, N, Khorami, E, Saki, N. Association between serum levels of interleukin-6 and stage of laryngeal cancer. Iran J Otorhinolaryngol 2015;27:199205 Google ScholarPubMed
40 Mojtahedi, Z, Khademi, B, Hashemi, SB, Abtahi, SM, Ghasemi, MA, Fattahi, MJ et al. Serum interleukin-6 concentration, but not interleukin-18, is associated with head and neck squamous cell carcinoma progression. Pathol Oncol Res 2011;17:710 CrossRefGoogle Scholar
41 Hao, W, Zhu, Y, Zhou, H. Prognostic value of interleukin-6 and interleukin-8 in laryngeal squamous cell cancer. Med Oncol 2013;30:333 CrossRefGoogle ScholarPubMed
42 Shkeir, O, Athanassiou-Papaefthymiou, M, Lapadatescu, M, Papagerakis, P, Czerwinski, MJ, Bradford, CR et al. In vitro cytokine release profile: predictive value for metastatic potential in head and neck squamous cell carcinoma. Head Neck 2013;35:1542–50CrossRefGoogle Scholar
43 Whiteside, TL. The tumor microenvironment and its role in promoting tumor growth. Oncogene 2008;27:5904–12CrossRefGoogle ScholarPubMed