Low-Dose Cyclophosphamide Synergizes with
Dendritic Cell-Based Immunotherapy in Antitumor Activity
Joris D. Veltman, Margaretha E. H. Lambers, Menno van Nimwegen, Sanne de Jong,
Rudi W. Hendriks, Henk C. Hoogsteden, Joachim G. J. V. Aerts, and Joost P. J. J. Hegmans
Department of Pulmonary Medicine, Erasmus Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
Correspondence should be addressed to Joost P. J. J. Hegmans,
j.hegmans@erasmusmc.nl
Received 30 November 2009; Revised 5 February 2010; Accepted 7 March 2010
Academic Editor: Zhengguo Xiao
Copyright © 2010 Joris D. Veltman et al.
This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor’s offensive repertoire that
suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We
studied the effect of low-dose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success
rate of dendritic cell immunotherapy could be improved. For this, mesothelioma tumor-bearing mice were treated with dendritic
cell-based immunotherapy alone or in combination with low-dose of cyclophosphamide. Proportions of regulatory T cells and
the cytotoxic T cell functions at different stages of disease were analyzed. We found that low-dose cyclophosphamide induced
beneficial immunomodulatory effects by preventing the induction of Tregs, and as a consequence, cytotoxic T cell function was
no longer affected. Addition of cyclophosphamide improved immunotherapy leading to an increased median and overall survival.
Future studies are needed to address the usefulness of this combination treatment for mesothelioma patients.
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