| Autor: |
Ge, Yingzi, Domschke, Christoph, Stoiber, Natalija, Schott, Sarah, Heil, Joerg, Rom, Joachim, Blumenstein, Maria, Thum, Janina, Sohn, Christof, Schneeweiss, Andreas, Beckhove, Philipp, Schuetz, Florian |
| Předmět: |
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| Zdroj: |
Cancer Immunology, Immunotherapy; Mar2012, Vol. 61 Issue 3, p353-362, 10p |
| Abstrakt: |
Severe immune suppression is frequent in late-stage tumor patients and promotes tumor immune evasion and subsequent tumor progression. Regulatory T cells (Treg) are major suppressors of anti-tumor immune responses. Therefore, targeting of Treg has become a key goal of anti-tumor therapy. Several preclinical and clinical observations suggest that Treg can be depleted by cyclophosphamide. Over a period of 3 months, we investigated the effect of metronomic low-dose cyclophosphamide on Treg numbers, suppressive capacity and proliferation on endogenous anti-tumor T-cell responses and on their correlation to clinical outcome in 12 patients with treatment-refractory metastasized breast cancer who received single-agent 50 mg cyclophosphamide p.o. daily. Cyclophosphamide treatment initially caused a significant reduction in circulating Treg by more than 40% ( P = 0.002). However, Treg numbers completely recovered during the treatment due to increased proliferative activity and maintained their suppressive capacity. Treg depletion coincided with a strong increase in breast tumor-reactive T cells ( P = 0.03) that remained at high levels during the whole period. Numbers of tumor-reactive T cells but not of Treg correlated with disease stabilization ( P = 0.03) and overall survival ( P = 0.027). We conclude that metronomic low-dose cyclophosphamide only transiently reduces Treg but induces stable tumor-specific T-cell responses, which correlate with improved clinical outcome in advanced-stage breast cancer patients. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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