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
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.
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.