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. 2015 Oct 1;8(10):13241-8.
eCollection 2015.

Expression of Sirt1 and FoxP3 in classical Hodgkin lymphoma and tumor infiltrating lymphocytes: Implications for immune dysregulation, prognosis and potential therapeutic targeting

Andrés E Quesada  1 , Binara Assylbekova  1 , Christine E Jabcuga  2 , Rongzhen Zhang  1 , Michael Covinsky  1 , Adan Rios  3 , Nghia D Nguyen  1 , Robert E Brown  1
Affiliations

Expression of Sirt1 and FoxP3 in classical Hodgkin lymphoma and tumor infiltrating lymphocytes: Implications for immune dysregulation, prognosis and potential therapeutic targeting

Andrés E Quesada et al. Int J Clin Exp Pathol. .

Abstract

Background: Hodgkin Reed-Sternberg (HRS) cells may promote differentiation of CD4+ naïve T cells toward both FoxP3+ T regulatory (Treg) cells and TIA-1+ cytotoxic T lymphocytes (CTL). Previous studies suggest that an overabundance of cytotoxic TIA-1+ cells in relation to FoxP3+ T reg cells portends unfavorable outcomes in classical Hodgkin lymphoma (cHL), raising the possibility that its pathogenesis may be related to immune dysregulation. Sirt1 deacetylates FoxP3 and leads to decreased Treg functionality. Our objective was to compare Sirt1 and FoxP3 expressions in Hodgkin lymphoma infiltrating lymphocytes (HLIL) and confirm Sirt1 expression in HRS cells.

Design: Immunohistochemical staining of paraffin-embedded tissue with antibodies to Sirt1, FoxP3, TIA-1, and CD8 was performed. Expression of Sirt1 was assessed in both the HRS cells and in the HLILs in twenty-four cases. Adequate tissue was available in 13 cHL cases to permit the enumeration of FoxP3, TIA-1 and CD8 by giving their percent staining of HLILs.

Results: In HLILs, nuclear expression of Sirt1 was 32-88% (mean 67%); FoxP3 expression was 9-40% (mean 23.9%); TIA-1 expression was 15-87% (mean 32%); and CD8 expression was 10-45% (mean = 31%). Sirt1 to FoxP3 ratio was 0.96-5.5 (mean 3.2). TIA-1 to FoxP3 ratio was 0.6-5.1 (mean 1.6). CD8 to FoxP3 ratio was 0.43-3.7 (mean 1.5). There was a difference of Sirt1 to FoxP3 ratios between remission and recurrence groups, being significantly higher in the recurrence group (P = 0.005). Sirt1 demonstrated high nuclear expression in the HRS cells of 21 out of 24 (88%) cases analyzed.

Conclusion: The relative overexpression of Sirt1 to FoxP3 in HLILs may be considered possible targets for immune modulation. Histone deacetylase inhibitors may increase the efficacy of existing treatment regimens by downregulating SIRT1 gene mRNA/Sirt1 protein function and together with rapamycin could expand the T regulatory/FoxP3 population and functionality and improve prognosis for remission in cHL. Targeting Sirt1 in the HRS cells may facilitate their ability to promote naïve T cell differentiation toward Treg cells over CTL.

Keywords: FoxP3; Hodgkin lymphoma; Sirt1; immune dysregulation; morphoproteomics.

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Figures

Figure 1
Figure 1
Sirt1 highly expressed in the nuclei of Hodgkin Reed-Sternberg cells by immunohistochemistry (A and B, arrows HR-S) and variably in the tumor infiltrating lymphocytes (B) from two cases of cHL in our study, contrast with negative control in (C) (original magnification, ×400 A ×600 B and C).
Figure 2
Figure 2
HLIL expression of (A) FoxP3, labeled as 9% staining in case 7, (B) FoxP3, labeled as 40% in case 11, (C) TIA-1, 15% in Case 4, (D) TIA-1, 87% Case 10, (E) Sirt1, 50% in Case 6, (F) Sirt1, 88% Sirt1 in Case 10. Images for CD8 not depicted (original magnification, ×400).
See this image and copyright information in PMC

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References

    1. Kuppers R. Molecular biology of Hodgkin’s lymphoma. Adv Cancer Res. 2002;84:277–312. - PubMed
    1. Kuppers R, Hansmann ML. The Hodgkin and Reed/Sternberg cell. Int J Biochem Cell Biol. 2005;37:511–517. - PubMed
    1. Hummel M, Ziemann K, Lammert H, Pileri S, Sabattini E, Stein H. Hodgkin’s disease with monoclonal and polyclonal populations of Reed-Sternberg cells. N Engl J Med. 1995;333:901–906. - PubMed
    1. Stein H, Hummel M. Cellular origin and clonality of classic Hodgkin’s lymphoma: immunophenotypic and molecular studies. Semin Hematol. 1999;36:233–241. - PubMed
    1. Kuppers R. Identifying the precursors of Hodgkin and Reed-Sternberg cells in Hodgkin’s disease: role of the germinal center in B-cell lymphomagenesis. J Acquir Immune Defic Syndr. 1999;21(Suppl 1):S74–79. - PubMed

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