Details

Autor(en) / Beteiligte

• Greten, Tim F
• Ormandy, Lars A
• Fikuart, Annika
• Höchst, Bastian
• Henschen, Sylvana
• Hörning, Monique
• Manns, Michael P
• Korangy, Firouzeh

Titel

Low-dose cyclophosphamide treatment impairs regulatory T cells and unmasks AFP-specific CD4+ T-cell responses in patients with advanced HCC

Ist Teil von

• Journal of immunotherapy (1997), 2010-02, Vol.33 (2), p.211-218

Ort / Verlag

United States

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• Immunotherapy represents a potential therapeutic option for patients with hepatocellular carcinoma (HCC). However, CD4CD25Foxp regulatory T cells, which suppress potential antigen-specific T-cell responses, are increased in patients with HCC and might impair the effect of an immune-based therapeutic approach. In this study, we demonstrate that depletion of regulatory T cells in vitro unmasks alpha-fetoprotein-specific T-cell responses in HCC patients. On the basis of these results, we performed a clinical trial, in which 13 patients with advanced HCC ineligible for any other type of treatment were treated with 150, 250, or 350 mg/m cyclophosphamide on day 1 and 29 to suppress regulatory T cells in these patients (NCT00396682). The primary end point of this trial was regulatory T-cell number and function. Low-dose cyclophosphamide treatment (150 and 250 mg/m) induced a decrease in the absolute and relative frequency of CD4CD25Foxp regulatory T cells in peripheral blood on days 8 and 29. Suppressor function of regulatory T cells was impaired after treatment of patients with 250 mg/m on days 8 and 21. Finally, alpha-fetoprotein-specific T-cell responses were unmasked in 6/13 treated patients. In summary, systemic treatment of HCC patients with low-dose cyclophosphamide decreases the frequency and suppressor function of circulating CD4CD25Foxp regulatory T cells in peripheral blood and could be used in combination with immunotherapeutic approaches in HCC.