Metronomic cyclophosphamide treatment in metastasized breast cancer patients: immunological effects and clinical outcome
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 pre...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
2012
|
| In: |
Cancer immunology immunotherapy
Year: 2011, Volume: 61, Issue: 3, Pages: 353-362 |
| ISSN: | 1432-0851 |
| DOI: | 10.1007/s00262-011-1106-3 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1007/s00262-011-1106-3 Verlag, Volltext: https://link.springer.com/article/10.1007/s00262-011-1106-3 
|
| Author Notes: | Yingzi Ge, Christoph Domschke, Natalija Stoiber, Sarah Schott, Joerg Heil, Joachim Rom, Maria Blumenstein, Janina Thum, Christof Sohn, Andreas Schneeweiss, Philipp Beckhove, Florian Schuetz |
| Summary: | 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. |
|---|---|
| Item Description: | Published online: 14 September 2011 Gesehen am 25.04.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1432-0851 |
| DOI: | 10.1007/s00262-011-1106-3 |