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.


CONCLUSIONS
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.
Griffiths
Richard W
RW
Department of Medical Oncology, Christie Research Centre, Paterson Institute for Cancer Research, Manchester, UK.
Elkord
Eyad
E
Gilham
David E
DE
Ramani
Vijay
V
Clarke
Noel
N
Stern
Peter L
PL
Hawkins
Robert E
RE
D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis*; D007680:Kidney Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*
D053645:Interleukin-2 Receptor alpha Subunit