open access

Vol 90, No 4 (2019)
ORIGINAL PAPERS Gynecology
Published online: 2019-04-29
Get Citation

Analysis of the treg cell population in the peripheral blood of ovarian cancer patients in relation to the long-term outcomes

Magdalena Maria Dutsch-Wicherek, Sebastian Szubert, Konrad Dziobek, Michal Wisniewski, Ewelina Lukaszewska, Lukasz Wicherek, Wojciech Jozwicki, Wojciech Rokita, Krzysztof Koper
DOI: 10.5603/GP.2019.0032
·
Pubmed: 31059109
·
Ginekol Pol 2019;90(4):179-184.

open access

Vol 90, No 4 (2019)
ORIGINAL PAPERS Gynecology
Published online: 2019-04-29

Abstract

Objectives: There is growing evidence that Treg cell infiltration into the cancer nest is associated with poor prognosis. How- ever, the Treg cell population in the peripheral blood may change when a different type of anticancer therapy is applied. Since Treg cells may support tumor growth by enhancing the suppressive profile of the cancer microenvironment, the assessment of Treg cells can bring to light important information regarding prognosis. Thus we decided to analyze the Treg cell population in the peripheral blood in relation to long-term outcomes in the group of patients with ovarian cancer. 

Material and methods: The 80 patients included in the study were treated surgically followed by chemiotherapy for ovar- ian cancer between October 2010 through May 2011.The peripheral blood samples from the patients were collected directly prior to chemotherapy. Information on any patients who died was retrieved from the database of the Cuiavia-Pomerania Regional Office of the National Health System of Poland. CD4+CD25+FOXP3+ lymphocytes T were assed by flow cytometry. We have analyzed the long term outcomes of treatment regarding to the level of Treg cells in peripheral blood. 

Results: We found that patients with serous adenocarcinomas had significantly higher Treg levels compared to those patients with non-serous types. Patients who had a higher percentage of Treg cells within the CD4+ cell population prior to the beginning of the treatment had worse long-term outcomes from the applied therapy. 

Conclusions: The assessment of Treg levels prior to the start of chemotherapy is clinically useful and may predict overall survival in ovarian cancer patients. 

Abstract

Objectives: There is growing evidence that Treg cell infiltration into the cancer nest is associated with poor prognosis. How- ever, the Treg cell population in the peripheral blood may change when a different type of anticancer therapy is applied. Since Treg cells may support tumor growth by enhancing the suppressive profile of the cancer microenvironment, the assessment of Treg cells can bring to light important information regarding prognosis. Thus we decided to analyze the Treg cell population in the peripheral blood in relation to long-term outcomes in the group of patients with ovarian cancer. 

Material and methods: The 80 patients included in the study were treated surgically followed by chemiotherapy for ovar- ian cancer between October 2010 through May 2011.The peripheral blood samples from the patients were collected directly prior to chemotherapy. Information on any patients who died was retrieved from the database of the Cuiavia-Pomerania Regional Office of the National Health System of Poland. CD4+CD25+FOXP3+ lymphocytes T were assed by flow cytometry. We have analyzed the long term outcomes of treatment regarding to the level of Treg cells in peripheral blood. 

Results: We found that patients with serous adenocarcinomas had significantly higher Treg levels compared to those patients with non-serous types. Patients who had a higher percentage of Treg cells within the CD4+ cell population prior to the beginning of the treatment had worse long-term outcomes from the applied therapy. 

Conclusions: The assessment of Treg levels prior to the start of chemotherapy is clinically useful and may predict overall survival in ovarian cancer patients. 

Get Citation

Keywords

regulatory T-cells; Tregs; ovarian cancer; tumor immunology

About this article
Title

Analysis of the treg cell population in the peripheral blood of ovarian cancer patients in relation to the long-term outcomes

Journal

Ginekologia Polska

Issue

Vol 90, No 4 (2019)

Pages

179-184

Published online

2019-04-29

DOI

10.5603/GP.2019.0032

Pubmed

31059109

Bibliographic record

Ginekol Pol 2019;90(4):179-184.

Keywords

regulatory T-cells
Tregs
ovarian cancer
tumor immunology

Authors

Magdalena Maria Dutsch-Wicherek
Sebastian Szubert
Konrad Dziobek
Michal Wisniewski
Ewelina Lukaszewska
Lukasz Wicherek
Wojciech Jozwicki
Wojciech Rokita
Krzysztof Koper

References (32)
  1. Nayama M, Collinet P, Salzet M, et al. Aspects immunologiques du cancer de l’ovaire : perspectives thérapeutiques. Journal de Gynécologie Obstétrique et Biologie de la Reproduction. 2016; 45(9): 1020–1036.
  2. Frydrychowicz M, Boruczkowski M, Kolecka-Bednarczyk A, et al. The Dual Role of Treg in Cancer. Scand J Immunol. 2017; 86(6): 436–443.
  3. Takeuchi Y, Nishikawa H. Roles of regulatory T cells in cancer immunity. Int Immunol. 2016; 28(8): 401–409.
  4. Zhou J, Li X, Wu X, et al. Exosomes Released from Tumor-Associated Macrophages Transfer miRNAs That Induce a Treg/Th17 Cell Imbalance in Epithelial Ovarian Cancer. Cancer Immunol Res. 2018; 6(12): 1578–1592.
  5. Li Li, Ma Y, Xu Y. Follicular regulatory T cells infiltrated the ovarian carcinoma and resulted in CD8 T cell dysfunction dependent on IL-10 pathway. Int Immunopharmacol. 2019; 68: 81–87.
  6. Wang WH, Xu HY, Zhao ZM, et al. Dynamic and significant changes of T-cell subgroups in breast cancer patients during surgery and chemotherapy. Int Immunopharmacol. 2018; 65: 279–283.
  7. Chen C, Chen D, Zhang Y, et al. Changes of CD4+CD25+FOXP3+ and CD8+CD28- regulatory T cells in non-small cell lung cancer patients undergoing surgery. Int Immunopharmacol. 2014; 18(2): 255–261.
  8. Jóźwicki W, Brożyna AA, Siekiera J, et al. Frequency of CD4+CD25+Foxp3+ cells in peripheral blood in relation to urinary bladder cancer malignancy indicators before and after surgical removal. Oncotarget. 2016; 7(10): 11450–11462.
  9. Cannioto RA, Sucheston-Campbell LE, Hampras S, et al. The Association of Peripheral Blood Regulatory T-Cell Concentrations With Epithelial Ovarian Cancer: A Brief Report. Int J Gynecol Cancer. 2017; 27(1): 11–16.
  10. Wu M, Chen X, Lou J, et al. Changes in regulatory T cells in patients with ovarian cancer undergoing surgery: Preliminary results. Int Immunopharmacol. 2017; 47: 244–250.
  11. Curiel TJ, Coukos G, Zou L, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004; 10(9): 942–949.
  12. Wiśniewski M, Koper K, Łukaszewska E, et al. Changes in the Treg lymphocyte population levels in patients being treated for ovarian cancer with chemotherapy. vol. 9. Medical Communications. 2009.
  13. Shaobin W, Yu X, Jiatian L, et al. Changes of CD4 T-cell subsets after radiofrequency ablation in lung cancer and its significance. J Cancer Res Ther. 2016; 12(Supplement): C166–C170.
  14. Munn DH, Sharma MD, Johnson TS. Treg Destabilization and Reprogramming: Implications for Cancer Immunotherapy. Cancer Res. 2018; 78(18): 5191–5199.
  15. Mhawech-Fauceglia P, Wang D, Ali L, et al. Intraepithelial T cells and tumor-associated macrophages in ovarian cancer patients. Cancer Immun. 2013; 13: 1.
  16. Leffers N, Gooden MJM, de Jong RA, et al. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother. 2009; 58(3): 449–459.
  17. Noordam L, Kaijen MEH, Bezemer K, et al. Low-dose cyclophosphamide depletes circulating naïve and activated regulatory T cells in malignant pleural mesothelioma patients synergistically treated with dendritic cell-based immunotherapy. Oncoimmunology. 2018; 7(12): e1474318.
  18. Wolf D, Wolf AM, Rumpold H, et al. The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res. 2005; 11(23): 8326–8331.
  19. Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003; 348(3): 203–213.
  20. Böhm S, Montfort A, Pearce OMT, et al. Neoadjuvant Chemotherapy Modulates the Immune Microenvironment in Metastases of Tubo-Ovarian High-Grade Serous Carcinoma. Clin Cancer Res. 2016; 22(12): 3025–3036.
  21. Chung YRi, Kim HJ, Jang MH, et al. Prognostic value of tumor infiltrating lymphocyte subsets in breast cancer depends on hormone receptor status. Breast Cancer Res Treat. 2017; 161(3): 409–420.
  22. Wouters M, Dijkgraaf EM, Kuijjer ML, et al. Interleukin-6 receptor and its ligand interleukin-6 are opposite markers for survival and infiltration with mature myeloid cells in ovarian cancer. Oncoimmunology. 2014; 3(12): e962397.
  23. Manku S, Wong W, Luo Z, et al. IL-6 expression is correlated with increased T-cell proliferation and survival in the arterial wall in giant cell arteritis. Cardiovasc Pathol. 2018; 33: 55–61.
  24. Zhang R, Tian A, Wang J, et al. miR26a modulates Th17/T reg balance in the EAE model of multiple sclerosis by targeting IL6. Neuromolecular Med. 2015; 17(1): 24–34.
  25. Toker A, Nguyen LT, Stone SC, et al. Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma. Clin Cancer Res. 2018; 24(22): 5685–5696.
  26. Bakos O, Lawson C, Rouleau S, et al. Combining surgery and immunotherapy: turning an immunosuppressive effect into a therapeutic opportunity. J Immunother Cancer. 2018; 6(1): 86.
  27. Sugiyama H, Gyulai R, Toichi E, et al. Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. J Immunol. 2005; 174(1): 164–173.
  28. Xu-Monette ZY, Zhang M, Li J, et al. PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response? Front Immunol. 2017; 8: 1597.
  29. Walentowicz-Sadlecka M, Dziobek K, Grabiec M, et al. The analysis of human leukocyte antigen-G level in patients with endometrial cancer by Western blot technique. American Journal of Reproductive Immunology. 2018; 81(1): e13070.
  30. Walentowicz-Sadlecka M, Koper A, Krystyna G, et al. The analysis of metallothionein immunoreactivity in stromal fibroblasts and macrophages in cases of uterine cervical carcinoma with respect to both the local and distant spread of the disease. Am J Reprod Immunol. 2013; 70(3): 253–261.
  31. Zhou J, Li X, Wu X, et al. Interaction between Treg cells and tumor-associated macrophages in the tumor microenvironment of epithelial ovarian cancer. Oncol Rep. 2016; 36(6): 3472–3478.
  32. Szymankiewicz M, Dziobek K, Sznajdorwska M, et al. An analysis of the influence of infection on overall survival rates, following modified posterior pelvic exenteration for advanced ovarian cancer. Ginekologia Polska. 2018; 89(11): 618–626.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk
tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl