Griffiths, RW, Elkord, E, Gilham, DE, Ramani, V, Clarke, N, Stern, PL and Hawkins, RE 2007, 'Frequency of regulatory T cells in renal cell carcinoma patients and investigation of correlation with survival' , Cancer Immunology, Immunotherapy, 56 (11) , pp. 1743-1753.
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Regulatory T cells are important in maintaining immune homeostasis, mediating peripheral tolerance and preventing autoimmunity. Increased frequencies of CD4(+)CD25(high )T regulatory (T(Reg)) cells have been documented in the peripheral blood of patients with several types of cancer consistent with a role in tumour escape from immunological control. We have investigated the presence of T(Reg) cells systemically and in situ in previously untreated patients with renal cell carcinoma (RCC). RESULTS: We have shown that there is a significant increased frequency of CD4(+)CD25(high) T cells in RCC patients (n = 49) compared to normal donors (n = 38), respectively, 2.47% versus 1.50%; P < 0.0001. We confirmed these data using the FOXP3 marker of T(Reg) cells in a subset of these patients and normal donors. The population of T(Reg) cells identified showed the expected phenotype with CD4(+)CD25(high) population in both RCC patients and normal donors contained higher proportions of CD45RO and GITR than CD4(+)CD25(-/low) populations and exhibiting suppressive activity in an anti-CD3 and anti-CD28 induced proliferation assay. CD4(+)FOXP3(+) T cells were detected in the tumour microenvironment by immunofluorescence and the numbers enumerated in lymphocytes recovered following enzymatic disaggregations of biopsies; their frequency was higher in the tumour than the peripheral blood of the same patients. The early follow up data show an association between higher peripheral blood regulatory T-cell count and adverse overall survival. CONCLUSION: These data confirm the increase of T(Reg) cells in RCC patients and provide impetus to further investigate modulation of T(Reg) activity in RCC patients as part of therapy.
|Themes:||Health and Wellbeing|
|Schools:||Schools > School of Environment and Life Sciences > Biomedical Research Centre
Schools > School of Environment and Life Sciences
|Journal or Publication Title:||Cancer Immunology, Immunotherapy|
|Depositing User:||E Elkord|
|Date Deposited:||13 Oct 2011 09:40|
|Last Modified:||20 Aug 2013 17:13|
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