Increase of CD4+CD25highFoxp3+ regulatory T cells in peripheral blood in patients with metastatic renal cell carcinoma treated with dendritic cell vaccination and low-dose IL-2

Abstract

16144 Background: CD4+CD25highFoxp3+ regulatory T cells (Treg) play an important role in the maintenance of immune tolerance and may be one of the obstacles of successful tumour immunotherapy. Method: The impact of administration of dendritic cell (DC) vaccination in combination with low-dose IL-2 in patients with metastatic renal cell carcinoma (mRCC) on the frequency of CD4+CD25highFoxp3+ regulatory T cells in peripheral blood was analysed. Results: The frequency of Treg cells increased more than 7-fold at the 4th vaccine (week four) compared to pre-treatment levels (p<0.0001). The frequency of Treg cells decreased at the 6th vaccine (week eight) compared to the 4th vaccine but remained significantly higher than the pre-treatment levels. In addition, longitudinal studies of Treg cell clonotypes in peripheral blood showed a remarkable heterogeneity over time and no persistent Treg cell clonotypes appeared, indicating that there is a rapid turn-over of Treg cell clonotypes in the peripheral circulation with disappearance of established clonotypes and appearance of new ones. Conclusion: These findings demonstrate that even low doses of IL-2 in combination with DC vaccination are able to expand CD4+CD25+Foxp3+ Treg cells in vivo in cancer patients. The decrease in frequency of Treg cells at the 6th vaccine where the patients had been off IL-2 treatment for only 8 days, indicates that the IL-2 induced effect on Tregs is reversible and declines shortly after termination of IL-2 treatment. Our data support the hypothesis that approaches combining DC-mediated immunotherapy and depletion of regulatory T cells may be necessary to enhance the ability of vaccination therapy to elicit effective anti- tumour responses in cancer patients. No significant financial relationships to disclose.