Metronomic cyclophosphamide treatment in metastasized breast cancer patients

• Verfasst von: Ge, Yingzi [VerfasserIn]
• Verfasst von: Domschke, Christoph [VerfasserIn]
• Verfasst von: Schott, Sarah [VerfasserIn]
• Verfasst von: Heil, Jörg [VerfasserIn]
• Verfasst von: Rom, Joachim [VerfasserIn]
• Verfasst von: Blumenstein, Maria [VerfasserIn]
• Verfasst von: Thum, Janina [VerfasserIn]
• Verfasst von: Sohn, Christof [VerfasserIn]
• Verfasst von: Schneeweiss, Andreas [VerfasserIn]
• Verfasst von: Beckhove, Philipp [VerfasserIn]
• Verfasst von: Schütz, Florian [VerfasserIn]
• Titel: Metronomic cyclophosphamide treatment in metastasized breast cancer patients
• Titelzusatz: immunological effects and clinical outcome
• Verf.angabe: Yingzi Ge, Christoph Domschke, Natalija Stoiber, Sarah Schott, Joerg Heil, Joachim Rom, Maria Blumenstein, Janina Thum, Christof Sohn, Andreas Schneeweiss, Philipp Beckhove, Florian Schuetz
• Jahr: 2012
• Jahr des Originals: 2011
• Umfang: 10 S.
• Fussnoten: Published online: 14 September 2011 ; Gesehen am 25.04.2018
• Titel Quelle: Enthalten in: Cancer immunology immunotherapy
• Ort Quelle: Berlin : Springer, 1976
• Jahr Quelle: 2012
• Band/Heft Quelle: 61(2012), 3, Seite 353-362
• ISSN Quelle: 1432-0851
• DOI: doi:10.1007/s00262-011-1106-3
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1572349778

Abstract

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.