Advertisement

Pathology & Oncology Research

, Volume 25, Issue 2, pp 647–652 | Cite as

The Effect of CD86 Expression on the Proliferation and the Survival of CLL Cells

  • Ferenc Takács
  • Csilla Tolnai-Kriston
  • Márk Hernádfői
  • Orsolya Szabó
  • Gábor Szalóki
  • Ágota Szepesi
  • Ágnes Czeti
  • András Matolcsy
  • Gábor BarnaEmail author
Original Article
  • 95 Downloads

Abstract

Micro-environment plays important role in the pathogenesis of CLL by providing protective niche for CLL cells. Several molecules play important role in communication between CLL cells and immune cells like CD86.Some of the data suggest that CLL patients with high CD86 level need earlier treatments and cells with higher CD86 expression has higher proliferation rate but the role of CD86 in the survival and proliferation of CLL cells is unclear. We investigated the effect of CD86 expression to CLL cells in 50 peripheral blood and 15 lymph node biopsy samples from CLL patients. Our results showed that the expressions of CD86 increased significantly after 7 day culturing in medium, or in the presence of bone marrow stromal cells (BMSCs). We found positive correlation between CD86 and CD23 expression (p < 0.05), but no correlation with other markers. Furthermore, no correlation were found between the CD86 expression and the proliferation of CLL cells. Analysis of clinical data showed that cases with high CD86 expression had lower level of serum lymphocyte count (p < 0.04) at the time of the diagnosis. CD86 shows multiple appearances in the lymph nodes containing pseudofollicules, but no correlation was found between CD86 positivity, and Ki67 positivity. Our results suggest that the use of CD86 molecule as a proliferation marker for CLL is highly questionable. However, the CD86 molecule may interfere with the immune system of patients with CLL by activating and depleting immune functions. That can be the reason why CD86 positivity may mean worse prognosis.

Keywords

CLL CD86 Micro-environment Proliferation marker 

Notes

Acknowledgments

This work was supported by the NVKP_16-1-2016-0004 grant of the Hungarian National Research, Development and Innovation Office (NFKIH).

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.

References

  1. 1.
    Zhang S, Kipps TJ (2014) The pathogenesis of chronic lymphocytic leukemia. Annu Rev Pathol 9:103–118CrossRefGoogle Scholar
  2. 2.
    Hallek M et al (2008) Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 111(12):5446–5456CrossRefGoogle Scholar
  3. 3.
    Gorczyca W (2010) Flow Cytometry in Neoplastic Hematology. Informa Healthcare London, LondonGoogle Scholar
  4. 4.
    Burger JA et al (2000) Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood 96(8):2655–2663Google Scholar
  5. 5.
    Panayiotidis P et al (1996) Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro. Br J Haematol 92(1):97–103CrossRefGoogle Scholar
  6. 6.
    Plander M et al (2011) Chronic lymphocytic leukemia cells induce anti-apoptotic effects of bone marrow stroma. Ann Hematol 90(12):1381–1390CrossRefGoogle Scholar
  7. 7.
    Alhakeem SS et al (2018) Chronic Lymphocytic Leukemia-Derived IL-10 Suppresses Antitumor Immunity. J Immunol 200(12):4180–4189CrossRefGoogle Scholar
  8. 8.
    Joss A et al (2000) IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation pathway. Eur J Immunol 30(6):1683–1690CrossRefGoogle Scholar
  9. 9.
    Brzostek J, Gascoigne NR, Rybakin V (2016) Cell Type-Specific Regulation of Immunological Synapse Dynamics by B7 Ligand Recognition. Front Immunol 7:24CrossRefGoogle Scholar
  10. 10.
    Dai ZS et al (2009) Defective expression and modulation of B7–2/CD86 on B cells in B cell chronic lymphocytic leukemia. Int J Hematol 89(5):656–663CrossRefGoogle Scholar
  11. 11.
    Huemer M et al (2014) AID induces intraclonal diversity and genomic damage in CD86(+) chronic lymphocytic leukemia cells. Eur J Immunol 44(12):3747–3757CrossRefGoogle Scholar
  12. 12.
    Swerdlow SH et al (2016) The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127(20):2375–2390CrossRefGoogle Scholar
  13. 13.
    Kriston C et al (2018) In contrast to high CD49d, low CXCR4 expression indicates the dependency of chronic lymphocytic leukemia (CLL) cells on the microenvironment. Ann Hematol 97(11):2145–2152Google Scholar
  14. 14.
    Kim SH, Lee CE (2011) Counter-regulation mechanism of IL-4 and IFN-α signal transduction through cytosolic retention of the pY-STAT6:pY-STAT2:p48 complex. Eur J Immunol 41(2):461–472CrossRefGoogle Scholar
  15. 15.
    Deszo EL et al (2004) IL-4-dependent CD86 expression requires JAK/STAT6 activation and is negatively regulated by PKCdelta. Cell Signal 16(2):271–280CrossRefGoogle Scholar
  16. 16.
    Hock BD, MacPherson SA, McKenzie JL (2017) Idelalisib and caffeine reduce suppression of T cell responses mediated by activated chronic lymphocytic leukemia cells. PLoS One 12(3):e0172858CrossRefGoogle Scholar
  17. 17.
    Gerdes J et al (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31(1):13–20CrossRefGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2018

Authors and Affiliations

  • Ferenc Takács
    • 1
  • Csilla Tolnai-Kriston
    • 1
  • Márk Hernádfői
    • 1
  • Orsolya Szabó
    • 1
  • Gábor Szalóki
    • 1
  • Ágota Szepesi
    • 1
  • Ágnes Czeti
    • 1
  • András Matolcsy
    • 1
  • Gábor Barna
    • 1
    Email author
  1. 1.1st Department of Pathology and Experimental Cancer ResearchSemmelweis UniversityBudapestHungary

Personalised recommendations