Frequency of regulatory T cells in renal cell carcinoma patients and investigation of correlation with survival
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Regulatory T cells are important in maintaining immune homeostasis, mediating peripheral tolerance and preventing autoimmunity. Increased frequencies of CD4+CD25high T regulatory (TReg) 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 TReg cells systemically and in situ in previously untreated patients with renal cell carcinoma (RCC).
We have shown that there is a significant increased frequency of CD4+CD25high 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 TReg cells in a subset of these patients and normal donors. The population of TReg cells identified showed the expected phenotype with CD4+CD25high 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.
These data confirm the increase of TReg cells in RCC patients and provide impetus to further investigate modulation of TReg activity in RCC patients as part of therapy.
KeywordsT regulatory cells Survival Renal cell carcinoma
This work was funded by Cancer Research UK. We are extremely grateful to all the volunteers who donated blood to this study. We are very grateful to Dr Thomas Southgate for optimising and performing the immunofluorescence for CD4 and FOXP3. Thanks also go to Andrea Spencer-Shaw, Caroline Hamer, Jackie Fenemore, Carmel Langan, Jackie O’Dwyer and Sue Neeson for their assistance in obtaining blood samples.
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