Skip to main content
Log in

Th17 cell expansion in gastric cancer may contribute to cancer development and metastasis

  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Th0 cells differentiate into Th1 or Th2 depending on multiple transcription factors acting on specific time points to regulate gene expression. Th17 cells, a subset of IL-17-producing T cells distinct from Th1 or Th2 cells has been described as key players in inflammation and autoimmune diseases as well as cancer development. In the present study, 66 patients with gastric cancer were included; the expression level of Th1- and Th17-related IFN-γ, IL-17, T-bet, RORγt in gastric cancer tissues and peripheral blood mononuclear cell (PBMC) were detected, analyzed the relationship between Th17 or Th1 infiltration and metastasis and explored the possible mechanism. Our results showed that IL-17 and RORγt expression were significantly increased in gastric cancer tissues and PBMC, especially, in metastasis patients; plasma IL-17 also increased; furthermore, the mRNA and protein levels of IL-1β, IL-21 and TGF-β were up-regulated. All the data indicated that Th17 was infiltrated the cancer tissue; IL-1β, IL-21 and TGF-β were also involved in gastric cancer development by promoting Th17 cell generation. From the above data, we speculated that Th17 cell expansion in gastric cancer may contribute to cancer development and metastasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Candido J, Hagemann T. Cancer-related inflammation. J Clin Immunol. 2013;33(Suppl 1):S79–84. doi:10.1007/s10875-012-9847-0.

    Article  PubMed  Google Scholar 

  2. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44. doi:10.1038/nature07205.

    Article  CAS  PubMed  Google Scholar 

  3. Sica A, Allavena P, Mantovani A. Cancer related inflammation: the macrophage connection. Cancer Lett. 2008;267(2):204–15. doi:10.1016/j.canlet.2008.03.028.

    Article  CAS  PubMed  Google Scholar 

  4. Zhu J, Paul WE. Heterogeneity and plasticity of T helper cells. Cell Res. 2010;20(1):4–12. doi:10.1038/cr.2009.138.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Zhu J, Paul WE. CD4 T cells: fates, functions, and faults. Blood. 2008;112(5):1557–69. doi:10.1182/blood-2008-05-078154.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol. 2007;81(1):1–5. doi:10.1189/jlb.0306164.

    Article  CAS  PubMed  Google Scholar 

  7. Kimura A, Kishimoto T. Th17 cells in inflammation. Int Immunopharmacol. 2011;11(3):319–22. doi:10.1016/j.intimp.2010.10.004.

    Article  CAS  PubMed  Google Scholar 

  8. Maddur MS, Miossec P, Kaveri SV, Bayry J. Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. Am J Pathol. 2012;181(1):8–18. doi:10.1016/j.ajpath.2012.03.044.

    Article  CAS  PubMed  Google Scholar 

  9. Wilke CM, Bishop K, Fox D, Zou W. Deciphering the role of Th17 cells in human disease. Trends Immunol. 2011;32(12):603–11. doi:10.1016/j.it.2011.08.003.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Ye J, Livergood RS, Peng G. The role and regulation of human Th17 cells in tumor immunity. Am J Pathol. 2013;182(1):10–20. doi:10.1016/j.ajpath.2012.08.041.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Zou W, Restifo NP. T(H)17 cells in tumour immunity and immunotherapy. Nat Rev Immunol. 2010;10(4):248–56. doi:10.1038/nri2742.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Kryczek I, Wei S, Gong W, Shu X, Szeliga W, Vatan L, et al. Cutting edge: IFN-gamma enables APC to promote memory Th17 and abate Th1 cell development. J Immunol. 2008;181(9):5842–6.

    Article  CAS  PubMed  Google Scholar 

  13. Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, et al. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood. 2009;114(6):1141–9. doi:10.1182/blood-2009-03-208249.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. 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. doi:10.1189/jlb.0609385.

    Article  CAS  PubMed  Google Scholar 

  15. Miyahara Y, Odunsi K, Chen W, Peng G, Matsuzaki J, Wang RF. Generation and regulation of human CD4+IL-17-producing T cells in ovarian cancer. Proc Natl Acad Sci USA. 2008;105(40):15505–10. doi:10.1073/pnas.0710686105.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. de Martel C, Forman D, Plummer M. Gastric cancer: epidemiology and risk factors. Gastroenterol Clin North Am. 2013;42(2):219–40. doi:10.1016/j.gtc.2013.01.003.

    Article  PubMed  Google Scholar 

  17. Alberts SR, Cervantes A, van de Velde CJ. Gastric cancer: epidemiology, pathology and treatment. Ann Oncol. 2003;14 Suppl 2:ii31–6.

    Google Scholar 

  18. Lilienfeld A. Epidemiology of gastric cancer. New Engl J Med. 1972;286(6):316–7. doi:10.1056/NEJM197202102860610.

    Article  CAS  PubMed  Google Scholar 

  19. Liu T, Peng L, Yu P, Zhao Y, Shi Y, Mao X, et al. Increased circulating Th22 and Th17 cells are associated with tumor progression and patient survival in human gastric cancer. J Clin Immunol. 2012;32(6):1332–9. doi:10.1007/s10875-012-9718-8.

    Article  PubMed  Google Scholar 

  20. Yamada Y, Saito H, Ikeguchi M. Prevalence and clinical relevance of Th17 cells in patients with gastric cancer. J Surg Res. 2012;178(2):685–91. doi:10.1016/j.jss.2012.07.055.

    Article  CAS  PubMed  Google Scholar 

  21. Li Q, Li Q, Chen J, Liu Y, Zhao X, Tan B, et al. Prevalence of Th17 and Treg cells in gastric cancer patients and its correlation with clinical parameters. Oncol Rep. 2013;. doi:10.3892/or.2013.2570.

    Google Scholar 

  22. Su Z, Sun C, Zhou C, Liu Y, Zhu H, Sandoghchian S, et al. HMGB1 blockade attenuates experimental autoimmune myocarditis and suppresses Th17-cell expansion. Eur J Immunol. 2011;41(12):3586–95. doi:10.1002/eji.201141879.

    Article  CAS  PubMed  Google Scholar 

  23. Greten TF, Zhao F, Gamrekelashvili J, Korangy F. Human Th17 cells in patients with cancer: Friends or foe? Oncoimmunology. 2012;1(8):1438–9. doi:10.4161/onci.21245.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Qian X, Gu L, Ning H, Zhang Y, Hsueh EC, Fu M, et al. Increased Th17 cells in the tumor microenvironment is mediated by IL-23 via tumor-secreted prostaglandin E2. J Immunol. 2013;190(11):5894–902. doi:10.4049/jimmunol.1203141.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, et al. IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature. 2008;454(7202):350–2. doi:10.1038/nature07021.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev. 2008;223:87–113. doi:10.1111/j.1600-065X.2008.00628.x.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Backert S, Clyne M, Tegtmeyer N. Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori. Cell Commun Signal CCS. 2011;9:28. doi:10.1186/1478-811X-9-28.

    Article  CAS  PubMed  Google Scholar 

  28. Asaoka Y, Ikenoue T, Koike K. New targeted therapies for gastric cancer. Expert Opin Investig Drugs. 2011;20(5):595–604. doi:10.1517/13543784.2011.566863.

    Article  CAS  PubMed  Google Scholar 

  29. Watanabe M, Kato J, Inoue I, Yoshimura N, Yoshida T, Mukoubayashi C, et al. Development of gastric cancer in nonatrophic stomach with highly active inflammation identified by serum levels of pepsinogen and Helicobacter pylori antibody together with endoscopic rugal hyperplastic gastritis. Int J Cancer. 2012;131(11):2632–42. doi:10.1002/ijc.27514.

    Article  CAS  PubMed  Google Scholar 

  30. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem. 2003;278(3):1910–4. doi:10.1074/jbc.M207577200.

    Article  CAS  PubMed  Google Scholar 

  31. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity. 2006;24(2):179–89. doi:10.1016/j.immuni.2006.01.001.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by National Natural Science Foundation of China (Grant No. 81370084, 81001319, 81101677), Postdoctoral foundation of China (2012M511705, 2013T60508), Postdoctoral foundation of Jiangsu Province (1102129C), Natural Science Foundation of Colleges and Universities in Jiangsu Province (Grant No. 10KJB310003) and High-Tech of Jiangsu University (Grant No. 11JDG128).

Conflict of interest

None to declare.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Wenlin Xu or Huaxi Xu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Su, Z., Sun, Y., Zhu, H. et al. Th17 cell expansion in gastric cancer may contribute to cancer development and metastasis. Immunol Res 58, 118–124 (2014). https://doi.org/10.1007/s12026-013-8483-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-013-8483-y

Keywords

Navigation