Journal of Isfahan Medical School

Journal of Isfahan Medical School

IFN-γ, IL-4 and IL-17 Concentration in Tumor Tissue, Adjacent Tumor Tissue and the Serums of Patients with Breast Cancer

Document Type : Original Article (s)

Authors
Alireza Andalib 1
Kamran Moghaddas 2
Farkhondeh Sharifi 3
Nafiseh Esmaeil 2
Seyed Javad Hasheminia 2
Mohammad Moazeni 4
1 Associate Professor, Department of Immunology, School of Medicine, Isfahan Univrsity of Medical Sciences, Isfahan, Iran
2 Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 General Surgeon, Farokhshar Imam Ali Hospital, Shahrekord, Iran
4 General Surgeon, Ayatolahe Kashani Hospital, Shahrekord, Iran
Abstract
Background: Tumor environment consists of various cells and cytokines. The cytokines are widely produced in the environment by tumor and immune cells. Tumor growth and development depends on the cytokines secreted in this environment. Cytokines have either pro-or anti-inflammatory activity as well as immunesurvilance stability which influence tumor progression in microenvironment.Methods: From 29 patients with breast cancer, 14 patients with malignant and 15 with benign tumors were considered. Specimens were collected from patients who were operated for breast cancer. Obtained tissues were kept at -80°C and then were prepared by homogenizer device. IFN-γ, IL-4 and IL-17 were measured in tumor tissue, adjacent tumor tissue, and patients’ serum using ELISA technique.Findings: The concentration of IL-4, IL-17, and IFN-γ were 112.3 ± 15.2, 16.9 ± 2.3, and 14.6 ± 3.8 pg/ml in malignant tissues, respectively. The concentration of IL-4 and IL-17 in tumor tissue, adjacent tumor tissue, and serum of patients with malignant tumors were higher than those with benign tumors.Conclusion: Our data indicates that elevated IL-4 and IL-17, but not IFN-γ, in tumor microenvironment may affect the malignancy progression.
Keywords
Cytokines
IFN-γ
IL-4
IL-17
Tumor
Breast tumors
  1. Kumar V, Cotran RS, Robbins SL. Robbins' Basic Pathology . 7th ed. London: WB. Saunders; 2003.
  2. Hagemann T, Robinson SC, Schulz M, Trumper L, Balkwill FR, Binder C. Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-alpha dependent up-regulation of matrix metalloproteases. Carcinogenesis 2004; 25(8): 1543-9.
  3. Lewis CE, Leek R, Harris A, McGee JO. Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages. J Leukoc Biol 1995; 57(5): 747-51.
  4. Seruga B, Zhang H, Bernstein LJ, Tannock IF. Cytokines and their relationship to the symptoms and outcome of cancer. Nat Rev Cancer 2008; 8(11): 887-99.
  5. Solinas G, Germano G, Mantovani A, Allavena P. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol 2009; 86(5): 1065-73.
  6. Oble DA, Loewe R, Yu P, Mihm MC, Jr. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human melanoma. Cancer Immun 2009; 9: 3.
  7. Solinas G, Germano G, Mantovani A, Allavena P. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol 2009; 86(5): 1065-73.
  8. Disis ML, Park KH. Immunomodulation of breast cancer via tumor antigen specific Th1. Cancer Res Treat 2009; 41(3): 117-21.
  9. Raman D, Baugher PJ, Thu YM, Richmond A. Role of chemokines in tumor growth. Cancer Lett 2007; 256(2): 137-65.
  10. Shurin MR, Lu L, Kalinski P, Stewart-Akers AM, Lotze MT. Th1/Th2 balance in cancer, transplantation and pregnancy. Springer Semin Immunopathol 1999; 21(3): 339-59.
  11. Alvarez DV. Interferon-gamma Receptor Deficiency (IFNgR deficiency). Charlotte, NC: Davidson College [Online] 2011. Available from: URL:
  12. http://www.bio.davidson.edu/courses/immunology/Students/spring2006/V_Alvarez/IFNgRdeficiency.html.
  13. Nam JS, Terabe M, Kang MJ, Chae H, Voong N, Yang YA, et al. Transforming growth factor beta subverts the immune system into directly promoting tumor growth through interleukin-17. Cancer Res 2008; 68(10): 3915-23.
  14. Zhou Y, Weyman CM, Liu H, Almasan A, Zhou A. IFN-gamma induces apoptosis in HL-60 cells through decreased Bcl-2 and increased Bak expression. J Interferon Cytokine Res 2008; 28(2): 65-72.
  15. Conticello C, Pedini F, Zeuner A, Patti M, Zerilli M, Stassi G, et al. IL-4 protects tumor cells from anti-CD95 and chemotherapeutic agents via up-regulation of antiapoptotic proteins. J Immunol 2004; 172(9): 5467-77.
  16. Gooch JL, Christy B, Yee D. STAT6 mediates interleukin-4 growth inhibition in human breast cancer cells. Neoplasia 2002; 4(4): 324-31.
  17. Zhu X, Mulcahy LA, Mohammed RA, Lee AH, Franks HA, Kilpatrick L, et al. IL-17 expression by breast-cancer-associated macrophages: IL-17 promotes invasiveness of breast cancer cell lines. Breast Cancer Res 2008; 10(6): R95.
  18. Aggarwal S, Gurney AL. IL-17: prototype member of an emerging cytokine family. J Leukoc Biol 2002; 71(1): 1-8.
  19. Kozlowski L, Zakrzewska I, Tokajuk P, Wojtukiewicz MZ. Concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) in blood serum of breast cancer patients. Rocz Akad Med Bialymst 2003; 48: 82-4.
  20. Camp BJ, Dyhrman ST, Memoli VA, Mott LA, Barth RJ, Jr. In situ cytokine production by breast cancer tumor-infiltrating lymphocytes. Ann Surg Oncol 1996; 3(2): 176-84.
  21. Aspord C, Pedroza-Gonzalez A, Gallegos M, Tindle S, Burton EC, Su D, et al. Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development. J Exp Med 2007; 204(5): 1037-47.
  22. Alimhojaeva LT. Pro and anti inflammatory cytokines level in patients suffering breast cancer [Online] 2010. [cited 2010 Apr 9]. Available from:URL: http://d.wanfangdata.com.cn/periodical_hwyy-z20100409.aspx
  23. Son GS, Ryu WS, Kim HY, Woo SU, Park KH, Bae JW. Immunologic Response to Mistletoe Extract (Viscum album L.) after Conventional Treatment in Patients with Operable Breast Cancer. J Breast Cancer 2010; 13(1): 14-8.
  24. Maniati E, Soper R, Hagemann T. Up for Mischief? IL-17/Th17 in the tumour micro-environment. Oncogene 2010; 29(42): 5653-62.
  25. Lyon DE, McCain NL, Walter J, Schubert C. Cytokine comparisons between women with breast cancer and women with a negative breast biopsy. Nurs Res 2008; 57(1): 51-8.
Journal of Isfahan Medical School
Volume 29, Issue 159 - Serial Number 159
September and October 2011
Pages 1669-1679

  • Receive Date 12 August 2011
  • Accept Date 06 April 2022