Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Article
  • Published:

IL-17 induces radiation resistance of B lymphoma cells by suppressing p53 expression and thereby inhibiting irradiation-triggered apoptosis

Cellular & Molecular Immunology volume 12, pages 366–372 (2015)Cite this article

Abstract

p53 is a well-known tumor suppressor. However, the regulatory mechanism(s) for p53 expression in B lymphoma cells, and the possible role of p53 in the development of the radioresistance in tumor cells are largely unknown. A human B lymphoma cell line, Karpas1106 (k1106), was used as a model of radioresistance. Apoptosis of k1106 cells was determined using flow cytometry. Expression of p53 was assessed using real time RT-PCR and western blotting. The results showed that irradiation at 8 Gy induced apoptosis in up to 40% of k1106 cells. At the same time, the irradiation markedly increased IL-6 production of the k1106 cells. When k1106 cells were cocultured with regulatory T cells (Tregs) and irradiated, the rate of apoptotic k1106 cells was significantly reduced, indicating an acquired resistance to irradiation. IL-6 derived from the irradiation-treated k1106 cells induced IL-17 expression in Tregs. The IL-17+Foxp3+ T cells suppressed p53 expression in k1106 cells. Collectively, irradiated k1106 cells induce the expression of IL-17 in Tregs, which interferes with the expression of p53 protein in k1106 cells and thereby represses irradiation-triggered apoptosis in k1106 cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Puvvada S, Kendrick S, Rimsza L . Molecular classification, pathway addiction, and therapeutic targeting in diffuse large B cell lymphoma. Cancer Genet 2013; 206: 257–265.

    Article  CAS  Google Scholar 

  2. Rivera-Rodriguez N, Cabanillas F . Recent advances in the management of mantle cell lymphoma. Curr Opin Oncol 2013; 25: 716–721.

    Article  CAS  Google Scholar 

  3. Domm JA, Thompson M, Kuttesch JF, Acra S, Frangoul H . Allogeneic bone marrow transplantation for chemotherapy-refractory hepatosplenic gamma delta T-cell lymphoma: case report and review of the literature. J Pediatr Hematol Oncol 2005; 27: 607–610.

    Article  Google Scholar 

  4. Isidori A, Piccaluga PP, Loscocco F, Guiducci B, Barulli S, Ricciardi T et al. High-dose therapy followed by stem cell transplantation in Hodgkin lymphoma: past and future. Expert Rev Hematol 2013; 6: 451–464.

    Article  CAS  Google Scholar 

  5. Nowarski RW . APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair. Blood 2012; 120: 366–375.

    Article  CAS  Google Scholar 

  6. Sghaier H, Ghedira K, Benkahla A, Barkallah I . Basal DNA repair machinery is subject to positive selection in ionizing-radiation-resistant bacteria. BMC Genomics 2008; 9: 297.

    Article  Google Scholar 

  7. Kim D, Chung K, Chung W, Bae S, Shin D, Hong S et al. Risk of secondary cancers from scattered radiation during intensity-modulated radiotherapies for hepatocellular carcinoma. Radiat Oncol 2014; 9: 109.

    Article  Google Scholar 

  8. Broustas CG, Lieberman HB . RAD9 enhances radioresistance of human prostate cancer cells through regulation of ITGB1 protein levels. Prostate 2014; 74: 1359–13570.

    Article  CAS  Google Scholar 

  9. Best G, Thompson P, Tam CS . Diagnostic techniques and therapeutic challenges in patients with TP53 dysfunctional chronic lymphocytic leukemia. Leuk Lymphoma 2012; 53: 2105–2115.

    Article  CAS  Google Scholar 

  10. de Viron E, Michaux L, Put N, Bontemps F, van den Neste E . Present status and perspectives in functional analysis of p53 in chronic lymphocytic leukemia. Leuk Lymphoma 2012; 53: 1445–1451.

    Article  CAS  Google Scholar 

  11. Li L, Boussiotis VA . The role of IL-17-producing Foxp3+CD4+ T cells in inflammatory bowel disease and colon cancer. Clin Immunol 2013; 148: 246–253.

    Article  CAS  Google Scholar 

  12. Wu C, Wang S, Wang F, Chen Q, Peng S, Zhang Y et al. Increased frequencies of T helper type 17 cells in the peripheral blood of patients with acute myeloid leukaemia. Clin Exp Immunol 2009; 158: 199–204.

    Article  CAS  Google Scholar 

  13. Teng MW, Vesely MD, Duret H, McLaughlin N, Towne JE, Schreiber RD et al. Opposing roles for IL-23 and IL-12 in maintaining occult cancer in an equilibrium state. Cancer Res 2012; 72: 3987–3996.

    Article  CAS  Google Scholar 

  14. Radosavljevic G, Ljujic B, Jovanovic I, Srzentic Z, Pavlovic S, Zdravkovic N et al. Interleukin-17 may be a valuable serum tumor marker in patients with colorectal carcinoma. Neoplasma 2010; 57: 135–144.

    Article  CAS  Google Scholar 

  15. Sun AM, Li CG, Han YQ, Liu QL, Xia Q, Yuan YW . X-ray irradiation promotes apoptosis of hippocampal neurons through up-regulation of Cdk5 and p25. Cancer Cell Int 2013; 13: 47.

    Article  Google Scholar 

  16. Oleinika K, Nibbs RJ, Graham GJ, Fraser AR . Suppression, subversion and escape: the role of regulatory T cells in cancer progression. Clin Exp Immunol 2013; 171: 36–45.

    Article  CAS  Google Scholar 

  17. Chen CC, Chen WC, Lu CH, Wang WH, Lin PY, Lee KD et al. Significance of interleukin-6 signaling in the resistance of pharyngeal cancer to irradiation and the epidermal growth factor receptor inhibitor. Int J Radiat Oncol Biol Phys 2010; 76: 1214–1224.

    Article  CAS  Google Scholar 

  18. Kimura A, Kishimoto T . IL-6: regulator of Treg/Th17 balance. Eur J Immunol 2010; 40: 1830–1835.

    Article  CAS  Google Scholar 

  19. Kim SH, Dass CR . p53-targeted cancer pharmacotherapy: move towards small molecule compounds. J Pharm Pharmacol 2011; 63: 603–610.

    Article  CAS  Google Scholar 

  20. Solanki AA, LeMieux MH, Chiu BC, Mahmood U, Hasan Y, Koshy M . Long-term outcomes in patients with early stage nodular lymphocyte-predominant hodgkin lymphoma treated with radiotherapy. PLoS ONE 2013; 8: e75336.

    Article  CAS  Google Scholar 

  21. Cheng JC, Bai A, Beckham TH, Marrison ST, Yount CL, Young K et al. Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse. J Clin Invest 2013; 123: 4344–4358.

    Article  CAS  Google Scholar 

  22. Trikha M, Corringham R, Klein B, Rossi JF . Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Clin Cancer Res 2003; 9: 4653–4665.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Wedlake LJ, Khan K, Ahmedi B, Thomas K, Abraham D, Andreyev N . Letter in response to article: a pilot study examining circulating interleukin-6 and transforming growth factor-beta levels during pelvic radiation therapy. Am J Clin Oncol 2013; 36: 102–103.

    Article  Google Scholar 

  24. Alberti L, Thomachot MC, Bachelot T, Menetrier-Caux C, Puisieux I, Blay JY . IL-6 as an intracrine growth factor for renal carcinoma cell lines. Int J Cancer 2004; 111: 653–661.

    Article  CAS  Google Scholar 

  25. Chen MF, Hsieh CC, Chen WC, Lai CH . Role of interleukin-6 in the radiation response of liver tumors. Int J Radiat Oncol Biol Phys 2012; 84: e621–e630.

    Article  CAS  Google Scholar 

  26. Gougelet A, Mansuy A, Blay JY, Alberti L, Vermot-Desroches C . Lymphoma and myeloma cell resistance to cytotoxic agents and ionizing radiations is not affected by exposure to anti-IL-6 antibody. PLoS ONE 2009; 4: e8026.

    Article  Google Scholar 

  27. Wang BQ, Zhang CM, Gao W, Wang XF, Zhang HL, Yang PC . Cancer-derived matrix metalloproteinase-9 contributes to tumor tolerance. J Cancer Res Clin Oncol 2011; 137: 1525–1533.

    Article  CAS  Google Scholar 

  28. Hemdan NY . Anti-cancer versus cancer-promoting effects of the interleukin-17-producing T helper cells. Immunol Lett 2013; 149: 123–133.

    Article  CAS  Google Scholar 

  29. Qu Y, Zhang B, Liu S, Zhang A, Wu T, Zhao Y . 2-Gy whole-body irradiation significantly alters the balance of CD4+CD25− T effector cells and CD4+CD25+Foxp3+ T regulatory cells in mice. Cell Mol Immunol 2010; 7: 419–427.

    Article  CAS  Google Scholar 

  30. Ganesan AP, Johansson M, Ruffell B, Beltran A, Lau J, Jablons DM et al. Tumor-infiltrating regulatory T cells inhibit endogenous cytotoxic T cell responses to lung adenocarcinoma. J Immunol 2013; 191: 2009–2017.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China

    Qingshan Li, Qinghua Du & Bizhen Yu

  2. Immunology Institute, Mount Sinai School of Medicine, New York, NY, USA

    Qingshan Li & Huabao Xiong

  3. Department of Hematology & Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China

    Xin Xu & Weijie Zhong

Authors
  1. Qingshan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xin Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weijie Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qinghua Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bizhen Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Huabao Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qingshan Li.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Q., Xu, X., Zhong, W. et al. IL-17 induces radiation resistance of B lymphoma cells by suppressing p53 expression and thereby inhibiting irradiation-triggered apoptosis. Cell Mol Immunol 12, 366–372 (2015). https://doi.org/10.1038/cmi.2014.122

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2014.122

Keywords

This article is cited by

Search

Advanced search

Quick links