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01.11.2007 | Original Article

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

verfasst von: Richard W. Griffiths, Eyad Elkord, David E. Gilham, Vijay Ramani, Noel Clarke, Peter L. Stern, Robert E. Hawkins

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 11/2007

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Abstract

Background

Regulatory T cells are important in maintaining immune homeostasis, mediating peripheral tolerance and preventing autoimmunity. Increased frequencies of CD4⁺CD25^highT 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.

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Titel: Frequency of regulatory T cells in renal cell carcinoma patients and investigation of correlation with survival
verfasst von: Richard W. Griffiths
Eyad Elkord
David E. Gilham
Vijay Ramani
Noel Clarke
Peter L. Stern
Robert E. Hawkins
Publikationsdatum: 01.11.2007
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 11/2007
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-007-0318-z

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