Frequency of regulatory T cells in renal cell carcinoma patients and investigation of correlation with survival

Background: 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.